IRAS01202+6133: A Possible Case of Protostellar Collapse Triggered by a Small HIIRegion

NASA Astrophysics Data System (ADS)

Kang, Sung-Ju; Kerton, C.

2012-01-01

The molecular gas surrounding an HII region is thought to be a place where star formation can be induced. One of the main questions in the study of star formation is how protostars accrete material from their parent molecular clouds and observations of infall motions are needed to provide direct evidence for accretion. This poster will present an analysis of submm spectroscopic observations of the submm/infrared source IRAS 01202+6133 located on the periphery of the HII region KR 120. HCO+(J=3-2) spectra of this source show a classic blue-dominated double-peaked profile indicative of infall motions that would be expected to occur in the envelope surrounding a young protostellar object. The HCO+ spectrum toward the core was fitted using models incorporating both outflow and infall components along with basic assumptions regarding excitation temperature trends within molecular cloud cores. Using the models, we derive physical properties of the infall kinematics and the envelope structure.

IRAS 01202+6133 : A Possible Case of Protostellar Collapse Triggered by a Small HII Region

NASA Astrophysics Data System (ADS)

Kang, Sung-Ju; Kerton, C.

2012-01-01

The molecular gas surrounding an HII region is thought to be a place where star formation can be induced. One of the main questions in the study of star formation is how protostars accrete material from their parent molecular clouds and observations of infall motions are needed to provide direct evidence for accretion. This poster will present an analysis of submm spectroscopic observations of the submm/infrared source IRAS 01202+6133 located on the periphery of the HII region KR 120. HCO+(J=3-2) spectra of this source show a classic blue-dominated double-peaked profile indicative of infall motions that would be expected to occur in the envelope surrounding a young protostellar object. The HCO+ spectrum toward the core was fitted using models incorporating both outflow and infall components along with basic assumptions regarding excitation temperature trends within molecular cloud cores. Using the models, we derive physical properties of the infall kinematics and the envelope structure.

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

PubMed

Shannon, Paul; Markiel, Andrew; Ozier, Owen; Baliga, Nitin S; Wang, Jonathan T; Ramage, Daniel; Amin, Nada; Schwikowski, Benno; Ideker, Trey

2003-11-01

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

PubMed

Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

2016-04-01

With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

Role of Molecular Profiling in Soft Tissue Sarcoma.

PubMed

Lindsay, Timothy; Movva, Sujana

2018-05-01

Diagnosis and treatment of soft tissue sarcoma (STS) is a particularly daunting task, largely due to the profound heterogeneity that characterizes these malignancies. Molecular profiling has emerged as a useful tool to confirm histologic diagnoses and more accurately classify these malignancies. Recent large-scale, multiplatform analyses have begun the work of establishing a more complete understanding of molecular profiling in STS subtypes and to identify new molecular alterations that may guide the development of novel targeted therapies. This review provides a brief and general overview of the role that molecular profiling has in STS, highlighting select sarcoma subtypes that are notable for recent developments. The role of molecular profiling as it relates to diagnostic strategies is discussed, along with ways that molecular profiling may provide guidance for potential therapeutic interventions. Copyright © 2018 by the National Comprehensive Cancer Network.

Pragmatic precision oncology: the secondary uses of clinical tumor molecular profiling

PubMed Central

Thota, Ramya; Staggs, David B; Johnson, Douglas B; Warner, Jeremy L

2016-01-01

Background Precision oncology increasingly utilizes molecular profiling of tumors to determine treatment decisions with targeted therapeutics. The molecular profiling data is valuable in the treatment of individual patients as well as for multiple secondary uses. Objective To automatically parse, categorize, and aggregate clinical molecular profile data generated during cancer care as well as use this data to address multiple secondary use cases. Methods A system to parse, categorize and aggregate molecular profile data was created. A naÿve Bayesian classifier categorized results according to clinical groups. The accuracy of these systems were validated against a published expertly-curated subset of molecular profiling data. Results Following one year of operation, 819 samples have been accurately parsed and categorized to generate a data repository of 10,620 genetic variants. The database has been used for operational, clinical trial, and discovery science research. Conclusions A real-time database of molecular profiling data is a pragmatic solution to several knowledge management problems in the practice and science of precision oncology. PMID:27026612

Membrane Insertion Profiles of Peptides Probed by Molecular Dynamics Simulations

DTIC Science & Technology

2008-07-17

Membrane insertion profiles of peptides probed by molecular dynamics simulations In-Chul Yeh,* Mark A. Olson,# Michael S. Lee,*#§ and Anders...a methodology based on molecular dynamics simulation techniques to probe the insertion profiles of small peptides across the membrane interface. The...profiles of peptides probed by molecular dynamics simulations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

The Basic Metabolic Profile in Heart Failure-Marker and Modifier.

PubMed

Elfar, Ahmed; Sambandam, Kamalanathan K

2017-08-01

The physiologic determinants of each of the components of the basic metabolic profile in patients with heart failure will be explored. Additionally, the review will discuss the prognostic value of alterations in the basic metabolic profile as well as their effects on management. Abnormalities in the basic metabolic profile have significant correlation with clinical outcomes and can modify treatment in heart failure. Hypochloremia has recently received increased attention for these reasons. Elevated creatinine, increased blood urea nitrogen, hyponatremia, and hypochloremia correlate with worse mortality and diuretic resistance in heart failure. Hypokalemia, even when mild, has proven to be a worse clinical indicator than modest elevations in serum potassium. Hypochloremia is mechanistically linked to hyponatremia and metabolic alkalosis, but recent compelling data suggests that it can provide more discriminating prognostic information. Knowledge of the physiologic basis for each of these alterations informs their management.

Characterization of an Extremely Basic Protein Derived from Granulosis Virus Nucleocapsids †

PubMed Central

Tweeten, Kathleen A.; Bulla, Lee A.; Consigli, Richard A.

1980-01-01

Nucleocapsids were isolated from purified enveloped nucleocapsids of Plodia interpunctella granulosis virus by treatment with Nonidet P-40. When analyzed on sodium dodecyl sulfate-polyacrylamide gels, the nucleocapsids consisted of eight polypeptides. One of these, a major component with a molecular weight of 12,500 (VP12), was selectively extracted from the nucleocapsids with 0.25 M sulfuric acid. Its electrophoretic mobility on acetic acid-urea gels was intermediate to that of cellular histones and protamine. Amino acid analysis showed that 39% of the amino acid residues of VP12 were basic: 27% were arginine and 12% were histidine. The remaining residues consisted primarily of serine, valine, and isoleucine. Proteins of similar arginine content also were extracted from the granulosis virus of Pieris rapae and from the nuclear polyhedrosis viruses of Spodoptera frugiperda and Autographa californica. The basic polypeptide appeared to be virus specific because it was found in nucleocapsids and virus-infected cells but not in uninfected cells. VP12 was not present in polypeptide profiles of granulosis virus capsids, indicating that it was an internal or core protein of the nucleocapsids. Electron microscopic observations suggested that the basic protein was associated with the viral DNA in the form of a DNA-protein complex. Images PMID:16789190

Ionospheric E-region electron density and neutral atmosphere variations

NASA Technical Reports Server (NTRS)

Stick, T. L.

1976-01-01

Electron density deviations from a basic variation with the solar zenith angle were investigated. A model study was conducted in which the effects of changes in neutral and relative densities of atomic and molecular oxygen on calculated electron densities were compared with incoherent scatter measurements in the height range 100-117 km at Arecibo, Puerto Rico. The feasibility of determining tides in the neutral atmosphere from electron density profiles was studied. It was determined that variations in phase between the density and temperature variation and the comparable magnitudes of their components make it appear improbable that the useful information on tidal modes can be obtained in this way.

Molecular profiling--a tool for addressing emerging gaps in the comparative risk assessment of GMOs.

PubMed

Heinemann, Jack A; Kurenbach, Brigitta; Quist, David

2011-10-01

Assessing the risks of genetically modified organisms (GMOs) is required by both international agreement and domestic legislation. Many view the use of the "omics" tools for profiling classes of molecules as useful in risk assessment, but no consensus has formed on the need or value of these techniques for assessing the risks of all GMOs. In this and many other cases, experts support case-by-case use of molecular profiling techniques for risk assessment. We review the latest research on the applicability and usefulness of molecular profiling techniques for GMO risk assessment. As more and more kinds of GMOs and traits are developed, broader use of molecular profiling in a risk assessment may be required to supplement the comparative approach to risk assessment. The literature-based discussions on the use of profiling appear to have settled on two findings: 1. profiling techniques are reliable and relevant, at least no less so than other techniques used in risk assessment; and 2. although not required routinely, regulators should be aware of when they are needed. The dismissal of routine molecular profiling may be confusing to regulators who then lack guidance on when molecular profiling might be worthwhile. Molecular profiling is an important way to increase confidence in risk assessments if the profiles are properly designed to address relevant risks and are applied at the correct stage of the assessment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Are three generations of quantitative molecular methods sufficient in medical virology? Brief review.

PubMed

Clementi, Massimo; Bagnarelli, Patrizia

2015-10-01

In the last two decades, development of quantitative molecular methods has characterized the evolution of clinical virology more than any other methodological advancement. Using these methods, a great deal of studies has addressed efficiently in vivo the role of viral load, viral replication activity, and viral transcriptional profiles as correlates of disease outcome and progression, and has highlighted the physio-pathology of important virus diseases of humans. Furthermore, these studies have contributed to a better understanding of virus-host interactions and have sharply revolutionized the research strategies in basic and medical virology. In addition and importantly from a medical point of view, quantitative methods have provided a rationale for the therapeutic intervention and therapy monitoring in medically important viral diseases. Despite the advances in technology and the development of three generations of molecular methods within the last two decades (competitive PCR, real-time PCR, and digital PCR), great challenges still remain for viral testing related not only to standardization, accuracy, and precision, but also to selection of the best molecular targets for clinical use and to the identification of thresholds for risk stratification and therapeutic decisions. Future research directions, novel methods and technical improvements could be important to address these challenges.

Different Transcriptional Response to Xanthomonas citri subsp. citri between Kumquat and Sweet Orange with Contrasting Canker Tolerance

PubMed Central

Fu, Xing-Zheng; Gong, Xiao-Qing; Zhang, Yue-Xin; Wang, Yin; Liu, Ji-Hong

2012-01-01

Citrus canker disease caused by Xanthomonas citri subsp. citri (Xcc) is one of the most devastating biotic stresses affecting the citrus industry. Meiwa kumquat (Fortunella crassifolia) is canker-resistant, while Newhall navel orange (Citrus sinensis Osbeck) is canker-sensitive. To understand the molecular mechanisms underlying the differences in responses to Xcc, transcriptomic profiles of these two genotypes following Xcc attack were compared by using the Affymetrix citrus genome GeneChip. A total of 794 and 1324 differentially expressed genes (DEGs) were identified as canker-responsive genes in Meiwa and Newhall, respectively. Of these, 230 genes were expressed in common between both genotypes, while 564 and 1094 genes were only significantly expressed in either Meiwa or Newhall. Gene ontology (GO) annotation and Singular Enrichment Analysis (SEA) of the DEGs showed that genes related to the cell wall and polysaccharide metabolism were induced for basic defense in both Meiwa and Newhall, such as chitinase, glucanase and thaumatin-like protein. Moreover, apart from inducing basic defense, Meiwa showed specially upregulated expression of several genes involved in the response to biotic stimulus, defense response, and cation binding as comparing with Newhall. And in Newhall, abundant photosynthesis-related genes were significantly down-regulated, which may be in order to ensure the basic defense. This study revealed different molecular responses to canker disease in Meiwa and Newhall, affording insight into the response to canker and providing valuable information for the identification of potential genes for engineering canker tolerance in the future. PMID:22848606

Univariate and multivariate molecular spectral analyses of lipid related molecular structural components in relation to nutrient profile in feed and food mixtures

NASA Astrophysics Data System (ADS)

Abeysekara, Saman; Damiran, Daalkhaijav; Yu, Peiqiang

2013-02-01

The objectives of this study were (i) to determine lipid related molecular structures components (functional groups) in feed combination of cereal grain (barley, Hordeum vulgare) and wheat (Triticum aestivum) based dried distillers grain solubles (wheat DDGSs) from bioethanol processing at five different combination ratios using univariate and multivariate molecular spectral analyses with infrared Fourier transform molecular spectroscopy, and (ii) to correlate lipid-related molecular-functional structure spectral profile to nutrient profiles. The spectral intensity of (i) CH3 asymmetric, CH2 asymmetric, CH3 symmetric and CH2 symmetric groups, (ii) unsaturation (Cdbnd C) group, and (iii) carbonyl ester (Cdbnd O) group were determined. Spectral differences of functional groups were detected by hierarchical cluster analysis (HCA) and principal components analysis (PCA). The results showed that the combination treatments significantly inflicted modifications (P < 0.05) in nutrient profile and lipid related molecular spectral intensity (CH2 asymmetric stretching peak height, CH2 symmetric stretching peak height, ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak area). Ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak significantly correlated with nutrient profiles. Both PCA and HCA differentiated lipid-related spectrum. In conclusion, the changes of lipid molecular structure spectral profiles through feed combination could be detected using molecular spectroscopy. These changes were associated with nutrient profiles and functionality.

Pragmatic precision oncology: the secondary uses of clinical tumor molecular profiling.

PubMed

Rioth, Matthew J; Thota, Ramya; Staggs, David B; Johnson, Douglas B; Warner, Jeremy L

2016-07-01

Precision oncology increasingly utilizes molecular profiling of tumors to determine treatment decisions with targeted therapeutics. The molecular profiling data is valuable in the treatment of individual patients as well as for multiple secondary uses. To automatically parse, categorize, and aggregate clinical molecular profile data generated during cancer care as well as use this data to address multiple secondary use cases. A system to parse, categorize and aggregate molecular profile data was created. A naÿve Bayesian classifier categorized results according to clinical groups. The accuracy of these systems were validated against a published expertly-curated subset of molecular profiling data. Following one year of operation, 819 samples have been accurately parsed and categorized to generate a data repository of 10,620 genetic variants. The database has been used for operational, clinical trial, and discovery science research. A real-time database of molecular profiling data is a pragmatic solution to several knowledge management problems in the practice and science of precision oncology. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Quantum computational studies, spectroscopic (FT-IR, FT-Raman and UV-Vis) profiling, natural hybrid orbital and molecular docking analysis on 2,4 Dibromoaniline

NASA Astrophysics Data System (ADS)

Abraham, Christina Susan; Prasana, Johanan Christian; Muthu, S.; Rizwana B, Fathima; Raja, M.

2018-05-01

The research exploration will comprise of investigating the molecular structure, vibrational assignments, bonding and anti-bonding nature, nonlinear optical, electronic and thermodynamic nature of the molecule. The research is conducted at two levels: First level employs the spectroscopic techniques - FT-IR, FT-Raman and UV-Vis characterizing techniques; at second level the data attained experimentally is analyzed through theoretical methods using and Density Function Theories which involves the basic principle of solving the Schrodinger equation for many body systems. A comparison is drawn between the two levels and discussed. The probability of the title molecule being bio-active theoretically proved by the electrophilicity index leads to further property analyzes of the molecule. The target molecule is found to fit well with Centromere associated protein inhibitor using molecular docking techniques. Higher basis set 6-311++G(d,p) is used to attain results more concurrent to the experimental data. The results of the organic amine 2, 4 Dibromoaniline is analyzed and discussed.

An Integrated Visualization and Basic Molecular Modeling Laboratory for First-Year Undergraduate Medicinal Chemistry

ERIC Educational Resources Information Center

Hayes, Joseph M.

2014-01-01

A 3D model visualization and basic molecular modeling laboratory suitable for first-year undergraduates studying introductory medicinal chemistry is presented. The 2 h practical is embedded within a series of lectures on drug design, target-drug interactions, enzymes, receptors, nucleic acids, and basic pharmacokinetics. Serving as a teaching aid…

Molecular sled sequences are common in mammalian proteins.

PubMed

Xiong, Kan; Blainey, Paul C

2016-03-18

Recent work revealed a new class of molecular machines called molecular sleds, which are small basic molecules that bind and slide along DNA with the ability to carry cargo along DNA. Here, we performed biochemical and single-molecule flow stretching assays to investigate the basis of sliding activity in molecular sleds. In particular, we identified the functional core of pVIc, the first molecular sled characterized; peptide functional groups that control sliding activity; and propose a model for the sliding activity of molecular sleds. We also observed widespread DNA binding and sliding activity among basic polypeptide sequences that implicate mammalian nuclear localization sequences and many cell penetrating peptides as molecular sleds. These basic protein motifs exhibit weak but physiologically relevant sequence-nonspecific DNA affinity. Our findings indicate that many mammalian proteins contain molecular sled sequences and suggest the possibility that substantial undiscovered sliding activity exists among nuclear mammalian proteins. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Molecules of significance in planetary aeronomy

NASA Technical Reports Server (NTRS)

Mohan, H.

1979-01-01

This monograph is basically devoted to spectroscopic information of the molecules of planetary interest. Only those molecules have been dealt with which have been confirmed spectroscopically to be present in the atmosphere of major planets of our solar system and play an important role in the aeronomy of the respective planets. An introduction giving the general conditions of planets and their atmospheres including the gaseous molecules is given. Some typical planetary spectra is presented and supported with a discussion on some basic concepts of optical absorption and molecular parameters that are important to the study of planetary atmospheres. Quantities like dipole moments, transition probabilities, Einstein coefficients and line strengths, radiative life times, absorption cross sections, oscillator strengths, line widths and profiles, equivalent widths, growth curves, bond strengths, electronic transition moments, Franck-Condon factors and r-centroids, etc., are discussed. Spectroscopic information and relevant data of 6 diatomic (HF, HCL, CO, H2, O2, N2) and 6 polyatomic (CO2, N2), O3, HeO, NH3, CH4) molecules are presented.

Attention profiles in autism spectrum disorder and subtypes of attention-deficit/hyperactivity disorder.

PubMed

Boxhoorn, Sara; Lopez, Eva; Schmidt, Catharina; Schulze, Diana; Hänig, Susann; Freitag, Christine M

2018-03-06

Attention problems are observed in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Most neuropsychological studies that compared both disorders focused on complex executive functions (EF), but missed to contrast basic attention functions, as well as ASD- and ADHD subtypes. The present study compared EF as well as basic attention functioning of children with the combined subtype (ADHD-C), the predominantly inattentive subtype (ADHD-I), and autism spectrum disorder without ADHD (ASD-) with typically developing controls (TD). Basic attention functions and EF profiles were analysed by testing the comprehensive attention function model of van Zomeren and Brouwer using profile analysis. Additionally, neurocognitive impairments in ASD- and ADHD were regressed on dimensional measures of attention- and hyperactive-impulsive symptoms across and within groups. ADHD-C revealed a strong impairment across measures of EF compared to ASD- and TD. The ADHD-C profile furthermore showed disorder specific impairments in interference control, whereas the ASD- profile showed a disorder specific impairment in basic attention component divided attention. Attention- and hyperactive-impulsive symptom severity did not predict neurocognitive impairments across- or within groups. Study findings thus support disorder and subtype specific attention/EF profiles, which refute the idea of a continuum of ADHD-I, ADHD-C, and ASD with increasing neurocognitive impairments.

Univariate and multivariate molecular spectral analyses of lipid related molecular structural components in relation to nutrient profile in feed and food mixtures.

PubMed

Abeysekara, Saman; Damiran, Daalkhaijav; Yu, Peiqiang

2013-02-01

The objectives of this study were (i) to determine lipid related molecular structures components (functional groups) in feed combination of cereal grain (barley, Hordeum vulgare) and wheat (Triticum aestivum) based dried distillers grain solubles (wheat DDGSs) from bioethanol processing at five different combination ratios using univariate and multivariate molecular spectral analyses with infrared Fourier transform molecular spectroscopy, and (ii) to correlate lipid-related molecular-functional structure spectral profile to nutrient profiles. The spectral intensity of (i) CH(3) asymmetric, CH(2) asymmetric, CH(3) symmetric and CH(2) symmetric groups, (ii) unsaturation (CC) group, and (iii) carbonyl ester (CO) group were determined. Spectral differences of functional groups were detected by hierarchical cluster analysis (HCA) and principal components analysis (PCA). The results showed that the combination treatments significantly inflicted modifications (P<0.05) in nutrient profile and lipid related molecular spectral intensity (CH(2) asymmetric stretching peak height, CH(2) symmetric stretching peak height, ratio of CH(2) to CH(3) symmetric stretching peak intensity, and carbonyl peak area). Ratio of CH(2) to CH(3) symmetric stretching peak intensity, and carbonyl peak significantly correlated with nutrient profiles. Both PCA and HCA differentiated lipid-related spectrum. In conclusion, the changes of lipid molecular structure spectral profiles through feed combination could be detected using molecular spectroscopy. These changes were associated with nutrient profiles and functionality. Copyright © 2012 Elsevier B.V. All rights reserved.

Boolean logic tree of graphene-based chemical system for molecular computation and intelligent molecular search query.

PubMed

Huang, Wei Tao; Luo, Hong Qun; Li, Nian Bing

2014-05-06

The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analyzing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable "words" and chemical interactions as "syntax" logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in biosensing, nanotechnology, and drug delivery.

Comprehensive and quantitative proteomic analyses of zebrafish plasma reveals conserved protein profiles between genders and between zebrafish and human.

PubMed

Li, Caixia; Tan, Xing Fei; Lim, Teck Kwang; Lin, Qingsong; Gong, Zhiyuan

2016-04-13

Omic approaches have been increasingly used in the zebrafish model for holistic understanding of molecular events and mechanisms of tissue functions. However, plasma is rarely used for omic profiling because of the technical challenges in collecting sufficient blood. In this study, we employed two mass spectrometric (MS) approaches for a comprehensive characterization of zebrafish plasma proteome, i.e. conventional shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) for an overview study and quantitative SWATH (Sequential Window Acquisition of all THeoretical fragment-ion spectra) for comparison between genders. 959 proteins were identified in the shotgun profiling with estimated concentrations spanning almost five orders of magnitudes. Other than the presence of a few highly abundant female egg yolk precursor proteins (vitellogenins), the proteomic profiles of male and female plasmas were very similar in both number and abundance and there were basically no other highly gender-biased proteins. The types of plasma proteins based on IPA (Ingenuity Pathway Analysis) classification and tissue sources of production were also very similar. Furthermore, the zebrafish plasma proteome shares significant similarities with human plasma proteome, in particular in top abundant proteins including apolipoproteins and complements. Thus, the current study provided a valuable dataset for future evaluation of plasma proteins in zebrafish.

Comprehensive and quantitative proteomic analyses of zebrafish plasma reveals conserved protein profiles between genders and between zebrafish and human

PubMed Central

Li, Caixia; Tan, Xing Fei; Lim, Teck Kwang; Lin, Qingsong; Gong, Zhiyuan

2016-01-01

Omic approaches have been increasingly used in the zebrafish model for holistic understanding of molecular events and mechanisms of tissue functions. However, plasma is rarely used for omic profiling because of the technical challenges in collecting sufficient blood. In this study, we employed two mass spectrometric (MS) approaches for a comprehensive characterization of zebrafish plasma proteome, i.e. conventional shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) for an overview study and quantitative SWATH (Sequential Window Acquisition of all THeoretical fragment-ion spectra) for comparison between genders. 959 proteins were identified in the shotgun profiling with estimated concentrations spanning almost five orders of magnitudes. Other than the presence of a few highly abundant female egg yolk precursor proteins (vitellogenins), the proteomic profiles of male and female plasmas were very similar in both number and abundance and there were basically no other highly gender-biased proteins. The types of plasma proteins based on IPA (Ingenuity Pathway Analysis) classification and tissue sources of production were also very similar. Furthermore, the zebrafish plasma proteome shares significant similarities with human plasma proteome, in particular in top abundant proteins including apolipoproteins and complements. Thus, the current study provided a valuable dataset for future evaluation of plasma proteins in zebrafish. PMID:27071722

On a Molecular Basis, Investigate Association of Molecular Structure with Bioactive Compounds, Anti-Nutritional Factors and Chemical and Nutrient Profiles of Canola Seeds and Co-Products from Canola Processing: Comparison Crusher Plants within Canada and within China as well as between Canada and China.

PubMed

Gomaa, Walaa M S; Mosaad, Gamal M; Yu, Peiqiang

2018-04-21

The objectives of this study were to: (1) Use molecular spectroscopy as a novel technique to quantify protein molecular structures in relation to its chemical profiles and bioenergy values in oil-seeds and co-products from bio-oil processing. (2) Determine and compare: (a) protein molecular structure using Fourier transform infrared (FT/IR-ATR) molecular spectroscopy technique; (b) bioactive compounds, anti-nutritional factors, and chemical composition; and (c) bioenergy values in oil seeds (canola seeds), co-products (meal or pellets) from bio-oil processing plants in Canada in comparison with China. (3) Determine the relationship between protein molecular structural features and nutrient profiles in oil-seeds and co-products from bio-oil processing. Our results showed the possibility to characterize protein molecular structure using FT/IR molecular spectroscopy. Processing induced changes between oil seeds and co-products were found in the chemical, bioenergy profiles and protein molecular structure. However, no strong correlation was found between the chemical and nutrient profiles of oil seeds (canola seeds) and their protein molecular structure. On the other hand, co-products were strongly correlated with protein molecular structure in the chemical profile and bioenergy values. Generally, comparisons of oil seeds (canola seeds) and co-products (meal or pellets) in Canada, in China, and between Canada and China indicated the presence of variations among different crusher plants and bio-oil processing products.

Far-infrared heterodyne spectrometer

NASA Technical Reports Server (NTRS)

Boreiko, Rita T.; Betz, Al L.

1995-01-01

A far-infrared heterodyne spectrometer was designed and built by our group for observations of atomic and molecular lines from interstellar clouds. Linewidths as narrow as 1 km/s can be expected from such regions, and so the spectrometer is designed with sub-km/s resolution so that observed line profiles will be resolved. Since its debut on the Kuiper Airborne Observatory (KAO) in 1985, the instrument has been used in regular annual flight programs from both Moffett Field, CA and Christchurch, NZ. The basic plan of the spectrometer remains unchanged from the original design presented at the previous airborne science symposium. Numerous improvements and updates to the technical capability have of course been included over the many years of operational service.

Inelastic response of silicon to shock compression.

PubMed

Higginbotham, A; Stubley, P G; Comley, A J; Eggert, J H; Foster, J M; Kalantar, D H; McGonegle, D; Patel, S; Peacock, L J; Rothman, S D; Smith, R F; Suggit, M J; Wark, J S

2016-04-13

The elastic and inelastic response of [001] oriented silicon to laser compression has been a topic of considerable discussion for well over a decade, yet there has been little progress in understanding the basic behaviour of this apparently simple material. We present experimental x-ray diffraction data showing complex elastic strain profiles in laser compressed samples on nanosecond timescales. We also present molecular dynamics and elasticity code modelling which suggests that a pressure induced phase transition is the cause of the previously reported 'anomalous' elastic waves. Moreover, this interpretation allows for measurement of the kinetic timescales for transition. This model is also discussed in the wider context of reported deformation of silicon to rapid compression in the literature.

Lidar Measurements of Tropospheric Wind Profiles with the Double Edge Technique

NASA Technical Reports Server (NTRS)

Gentry, Bruce M.; Li, Steven X.; Korb, C. Laurence; Mathur, Savyasachee; Chen, Huailin

1998-01-01

Research has established the importance of global tropospheric wind measurements for large scale improvements in numerical weather prediction. In addition, global wind measurements provide data that are fundamental to the understanding and prediction of global climate change. These tasks are closely linked with the goals of the NASA Earth Science Enterprise and Global Climate Change programs. NASA Goddard has been actively involved in the development of direct detection Doppler lidar methods and technologies to meet the wind observing needs of the atmospheric science community. A variety of direct detection Doppler wind lidar measurements have recently been reported indicating the growing interest in this area. Our program at Goddard has concentrated on the development of the edge technique for lidar wind measurements. Implementations of the edge technique using either the aerosol or molecular backscatter for the Doppler wind measurement have been described. The basic principles have been verified in lab and atmospheric lidar wind experiments. The lidar measurements were obtained with an aerosol edge technique lidar operating at 1064 nm. These measurements demonstrated high spatial resolution (22 m) and high velocity sensitivity (rms variances of 0.1 m/s) in the planetary boundary layer (PBL). The aerosol backscatter is typically high in the PBL and the effects of the molecular backscatter can often be neglected. However, as was discussed in the original edge technique paper, the molecular contribution to the signal is significant above the boundary layer and a correction for the effects of molecular backscatter is required to make wind measurements. In addition, the molecular signal is a dominant source of noise in regions where the molecular to aerosol ratio is large since the energy monitor channel used in the single edge technique measures the sum of the aerosol and molecular signals. To extend the operation of the edge technique into the free troposphere we have developed a variation of the edge technique called the double edge technique. In this paper a ground based aerosol double edge lidar is described and the first measurements of wind profiles in the free troposphere obtained with this lidar will be presented.

Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer.

PubMed

Zardavas, Dimitrios; Piccart-Gebhart, Martine

2015-01-01

High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.

Authentication of forensic DNA samples.

PubMed

Frumkin, Dan; Wasserstrom, Adam; Davidson, Ariane; Grafit, Arnon

2010-02-01

Over the past twenty years, DNA analysis has revolutionized forensic science, and has become a dominant tool in law enforcement. Today, DNA evidence is key to the conviction or exoneration of suspects of various types of crime, from theft to rape and murder. However, the disturbing possibility that DNA evidence can be faked has been overlooked. It turns out that standard molecular biology techniques such as PCR, molecular cloning, and recently developed whole genome amplification (WGA), enable anyone with basic equipment and know-how to produce practically unlimited amounts of in vitro synthesized (artificial) DNA with any desired genetic profile. This artificial DNA can then be applied to surfaces of objects or incorporated into genuine human tissues and planted in crime scenes. Here we show that the current forensic procedure fails to distinguish between such samples of blood, saliva, and touched surfaces with artificial DNA, and corresponding samples with in vivo generated (natural) DNA. Furthermore, genotyping of both artificial and natural samples with Profiler Plus((R)) yielded full profiles with no anomalies. In order to effectively deal with this problem, we developed an authentication assay, which distinguishes between natural and artificial DNA based on methylation analysis of a set of genomic loci: in natural DNA, some loci are methylated and others are unmethylated, while in artificial DNA all loci are unmethylated. The assay was tested on natural and artificial samples of blood, saliva, and touched surfaces, with complete success. Adopting an authentication assay for casework samples as part of the forensic procedure is necessary for maintaining the high credibility of DNA evidence in the judiciary system.

[MUC4 research progress in tumor molecular markers].

PubMed

Zhu, Hua; You, Jinhui

2014-02-01

Mucin antigen 4 (MUC4) is a molecular marker for some malignant tumors for early tumor diagnosis, prognosis and targeted therapy. It provides a new research direction in tumor diagnosis and treatment that will have a wide application prospect. In recent years, there has been a large number of research reports on the basic and clini-a wide application prospect. In recent years, there has been a large number of research reports on the basic and clinical studies about MUC4, but the molecular imaging study about MUC4 is seldom reported. In this paper the recentcal studies about MUC4, but the molecular imaging study about MUC4 is seldom reported. In this paper the recent research about MUC4 on basic and clinical studies is briefly reviewed, and it is expected to promote the development of tumor molecular imaging.

Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

DTIC Science & Technology

2017-10-01

development and patterning, and to become more knowledgeable in molecular genetics and the pathology of human prostatic diseases. Specific Aims: 1...AWARD NUMBER: W81XWH-15-1-0661 TITLE: Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and...COVERED 30 Sept 2016 – 29 Sept 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Comprehensive Molecular Profiling of African-American Prostate Cancer to

Molecular basis of angiosperm tree architecture

USDA-ARS?s Scientific Manuscript database

The shoot architecture of trees greatly impacts orchard and forest management methods. Amassing greater knowledge of the molecular genetics behind tree form can benefit these industries as well as contribute to basic knowledge of plant developmental biology. This review covers basic components of ...

The Basic Principles of FDG-PET/CT Imaging.

PubMed

Basu, Sandip; Hess, Søren; Nielsen Braad, Poul-Erik; Olsen, Birgitte Brinkmann; Inglev, Signe; Høilund-Carlsen, Poul Flemming

2014-10-01

Positron emission tomography (PET) imaging with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) forms the basis of molecular imaging. FDG-PET imaging is a multidisciplinary undertaking that requires close interdisciplinary collaboration in a broad team comprising physicians, technologists, secretaries, radio-chemists, hospital physicists, molecular biologists, engineers, and cyclotron technicians. The aim of this review is to provide a brief overview of important basic issues and considerations pivotal to successful patient examinations, including basic physics, instrumentation, radiochemistry, molecular and cell biology, patient preparation, normal distribution of tracer, and potential interpretive pitfalls. Copyright © 2014 Elsevier Inc. All rights reserved.

Tuberculosis patients co-infected with Mycobacterium bovis and Mycobacterium tuberculosis in an urban area of Brazil.

PubMed

Silva, Marcio Roberto; Rocha, Adalgiza da Silva; da Costa, Ronaldo Rodrigues; de Alencar, Andrea Padilha; de Oliveira, Vania Maria; Fonseca Júnior, Antônio Augusto; Sales, Mariana Lázaro; Issa, Marina de Azevedo; Filho, Paulo Martins Soares; Pereira, Omara Tereza Vianello; dos Santos, Eduardo Calazans; Mendes, Rejane Silva; Ferreira, Angela Maria de Jesus; Mota, Pedro Moacyr Pinto Coelho; Suffys, Philip Noel; Guimarães, Mark Drew Crosland

2013-05-01

In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials.

A Panchromatic Study of Molecular Gas in the Protoplanetary System RY Lupi

NASA Astrophysics Data System (ADS)

Arulanantham, Nicole; France, Kevin; Hoadley, Keri

2018-01-01

To understand how planet formation occurs in protoplanetary disks, we must first characterize the behavior of material within 10 AU of the central star. We present a study of molecular gas at these radii in the disk around the young star RY Lupi, through spectra from HST-COS, HST-STIS, and VLT-CRIRES. We model the radial distribution of flux from hot (T ~ 2000 K) molecular gas in a surface layer between r = 0.1-10 AU, as traced by LyA-pumped H2. The result indicates that the H2 emission originates in a narrow ring centered at 1 AU, with a sharp decline in flux at r < 0.1 AU that is consistent with what is expected for transitional disks. When we adopt a more basic approach to evaulate the shapes of the emission lines, we find that a two-component Gaussian profile assuming two rings of gas in the inner disk provides a statistically better fit to the H2 emission lines than the single-component model of a smooth disk. This two-component profile includes broad (FWHMbroad, H2 = 105 +/- 15 km/s) and narrow (FWHMnarrow, H2 = 43 +/- 13 km/s) lines, corresponding to average gas radii of ~ 0.4 AU and ~ 3 AU. An analysis of the spatial origin of 4.7 micron 12CO emission shows that this population of warm (T ~ 1500 K) gas also produces two-component emission line profiles ( ~ 0.4 AU, ~ 15 AU), indicating again that the inner disk is radially stratified. Despite the evidence that this is a transitional disk system, we detect UV CO absorption that is not typically seen in more evolved systems. We model these features along with IR CO absorptions to constrain the properties of the cooler (T ~ 100-300 K) disk atmosphere.

The Strong Ring: A Basic Interest Model of Occupational Structure

ERIC Educational Resources Information Center

Armstrong, Patrick Ian; Smith, Thomas J.; Donnay, David A. C.; Rounds, James

2004-01-01

A classification system and spatial map of occupations were developed using the Basic Interest Scale profiles of 198 occupational incumbent samples (31,010 women; 32,421 men) from the Strong Interest Inventory. Profile shape was found to be similar for incumbents of both genders, allowing for an analysis of combined-gender samples. Using…

A study of some non-equilibrium driven models and their contribution to the understanding of molecular motors

NASA Astrophysics Data System (ADS)

Mazilu, Irina; Gonzalez, Joshua

2008-03-01

From the point of view of a physicist, a bio-molecular motor represents an interesting non-equilibrium system and it is directly amenable to an analysis using standard methods of non-equilibrium statistical physics. We conduct a rigorous Monte Carlo study of three different driven lattice gas models that retain the basic behavior of three types of cytoskeletal molecular motors. Our models incorporate novel features such as realistic dynamics rules and complex motor-motor interactions. We are interested to have a deeper understanding of how various parameters influence the macroscopic behavior of these systems, what is the density profile and if the system undergoes a phase transition. On the analytical front, we computed the steady-state probability distributions exactly for the one of the models using the matrix method that was established in 1993 by B. Derrida et al. We also explored the possibilities offered by the ``Bethe ansatz'' method by mapping some well studied spin models into asymmetric simple exclusion models (already analyzed using computer simulations), and to use the results obtained for the spin models in finding an exact solution for our problem. We have exhaustive computational studies of the kinesin and dynein molecular motor models that prove to be very useful in checking our analytical work.

Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity

PubMed Central

Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Karger, David R.; Lindquist, Susan; Fraenkel, Ernest

2009-01-01

Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens, yet the functional roles of the genes identified by these assays often remain enigmatic. By comparing the results of these two assays across various cellular responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify response regulators, while mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We harnessed this approach to reveal cellular pathways related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative disorders including Parkinson disease. For this we screened an established yeast model for alpha-synuclein toxicity to identify genes that when overexpressed alter cellular survival. Application of our algorithm to these data and data from mRNA profiling provided functional explanations for many of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470

Molecular and Cellular Designs of Insect Taste Receptor System

PubMed Central

Isono, Kunio; Morita, Hiromi

2010-01-01

The insect gustatory receptors (GRs) are members of a large G-protein coupled receptor family distantly related to the insect olfactory receptors. They are phylogenetically different from taste receptors of most other animals. GRs are often coexpressed with other GRs in single receptor neurons. Taste receptors other than GRs are also expressed in some neurons. Recent molecular studies in the fruitfly Drosophila revealed that the insect taste receptor system not only covers a wide ligand spectrum of sugars, bitter substances or salts that are common to mammals but also includes reception of pheromone and somatosensory stimulants. However, the central mechanism to perceive and discriminate taste information is not yet elucidated. Analysis of the primary projection of taste neurons to the brain shows that the projection profiles depend basically on the peripheral locations of the neurons as well as the GRs that they express. These results suggest that both peripheral and central design principles of insect taste perception are different from those of olfactory perception. PMID:20617187

The Social Profile of Students in Basic General Education in Ecuador: A Data Analysis

ERIC Educational Resources Information Center

Buri, Olga Elizabeth Minchala; Stefos, Efstathios

2017-01-01

The objective of this study is to examine the social profile of students who are enrolled in Basic General Education in Ecuador. Both a descriptive and multidimensional statistical analysis was carried out based on the data provided by the National Survey of Employment, Unemployment and Underemployment in 2015. The descriptive analysis shows the…

Subgroups of Adult Basic Education Learners with Different Profiles of Reading Skills

ERIC Educational Resources Information Center

MacArthur, Charles A.; Konold, Timothy R.; Glutting, Joseph J.; Alamprese, Judith A.

2012-01-01

The purpose of this study was to identify subgroups of adult basic education (ABE) learners with different profiles of skills in the core reading components of decoding, word recognition, spelling, fluency, and comprehension. The analysis uses factor scores of those 5 reading components from on a prior investigation of the reliability and…

Conserved Gene Expression Programs in Developing Roots from Diverse Plants.

PubMed

Huang, Ling; Schiefelbein, John

2015-08-01

The molecular basis for the origin and diversification of morphological adaptations is a central issue in evolutionary developmental biology. Here, we defined temporal transcript accumulation in developing roots from seven vascular plants, permitting a genome-wide comparative analysis of the molecular programs used by a single organ across diverse species. The resulting gene expression maps uncover significant similarity in the genes employed in roots and their developmental expression profiles. The detailed analysis of a subset of 133 genes known to be associated with root development in Arabidopsis thaliana indicates that most of these are used in all plant species. Strikingly, this was also true for root development in a lycophyte (Selaginella moellendorffii), which forms morphologically different roots and is thought to have evolved roots independently. Thus, despite vast differences in size and anatomy of roots from diverse plants, the basic molecular mechanisms employed during root formation appear to be conserved. This suggests that roots evolved in the two major vascular plant lineages either by parallel recruitment of largely the same developmental program or by elaboration of an existing root program in the common ancestor of vascular plants. © 2015 American Society of Plant Biologists. All rights reserved.

Flower Development

PubMed Central

Alvarez-Buylla, Elena R.; Benítez, Mariana; Corvera-Poiré, Adriana; Chaos Cador, Álvaro; de Folter, Stefan; Gamboa de Buen, Alicia; Garay-Arroyo, Adriana; García-Ponce, Berenice; Jaimes-Miranda, Fabiola; Pérez-Ruiz, Rigoberto V.; Piñeyro-Nelson, Alma; Sánchez-Corrales, Yara E.

2010-01-01

Flowers are the most complex structures of plants. Studies of Arabidopsis thaliana, which has typical eudicot flowers, have been fundamental in advancing the structural and molecular understanding of flower development. The main processes and stages of Arabidopsis flower development are summarized to provide a framework in which to interpret the detailed molecular genetic studies of genes assigned functions during flower development and is extended to recent genomics studies uncovering the key regulatory modules involved. Computational models have been used to study the concerted action and dynamics of the gene regulatory module that underlies patterning of the Arabidopsis inflorescence meristem and specification of the primordial cell types during early stages of flower development. This includes the gene combinations that specify sepal, petal, stamen and carpel identity, and genes that interact with them. As a dynamic gene regulatory network this module has been shown to converge to stable multigenic profiles that depend upon the overall network topology and are thus robust, which can explain the canalization of flower organ determination and the overall conservation of the basic flower plan among eudicots. Comparative and evolutionary approaches derived from Arabidopsis studies pave the way to studying the molecular basis of diverse floral morphologies. PMID:22303253

Field Effect Sensors for Nucleic Acid Detection: Recent Advances and Future Perspectives

PubMed Central

Veigas, Bruno; Fortunato, Elvira; Baptista, Pedro V.

2015-01-01

In the last decade the use of field-effect-based devices has become a basic structural element in a new generation of biosensors that allow label-free DNA analysis. In particular, ion sensitive field effect transistors (FET) are the basis for the development of radical new approaches for the specific detection and characterization of DNA due to FETs’ greater signal-to-noise ratio, fast measurement capabilities, and possibility to be included in portable instrumentation. Reliable molecular characterization of DNA and/or RNA is vital for disease diagnostics and to follow up alterations in gene expression profiles. FET biosensors may become a relevant tool for molecular diagnostics and at point-of-care. The development of these devices and strategies should be carefully designed, as biomolecular recognition and detection events must occur within the Debye length. This limitation is sometimes considered to be fundamental for FET devices and considerable efforts have been made to develop better architectures. Herein we review the use of field effect sensors for nucleic acid detection strategies—from production and functionalization to integration in molecular diagnostics platforms, with special focus on those that have made their way into the diagnostics lab. PMID:25946631

Accelerated molecular dynamics simulations of protein folding.

PubMed

Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

2015-07-30

Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

Urtica dioica pollen allergy: Clinical, biological, and allergomics analysis.

PubMed

Tiotiu, Angelica; Brazdova, Andrea; Longé, Cyril; Gallet, Patrice; Morisset, Martine; Leduc, Virginie; Hilger, Christiane; Broussard, Cédric; Couderc, Rémy; Sutra, Jean-Pierre; Sénéchal, Hélène; Poncet, Pascal

2016-11-01

The most emblematic members of Urticaceae at allergic risk level are wall pellitories (Parietaria), whereas nettle (Urtica) pollen is considered as poorly allergenic. No allergen from nettle pollen has yet been characterized, whereas 4 are listed for Parietaria pollen by the International Union of Immunological Societies. Clinical and biological profiles of 2 adult men who developed symptoms against nettle pollen and/or leaves were studied. To characterize the allergic reaction and identify the potential nettle pollen sensitizing allergens. IgE-mediated reaction to nettle pollen extract was evaluated by skin prick test, immunoassay, nasal provocation, and basophil activation test. To characterize specific nettle pollen allergens, an allergomic (IgE immunoproteomic) analysis was performed combining 1- and 2-dimensional electrophoresis, IgE immunoblots of nettle pollen extract, identification of allergens by mass spectrometry, and database queries. The results of biological and immunochemical analyses revealed that the allergic rhinitis was due to Urtica dioica pollen in both patients. The allergomic analysis of nettle pollen extract allowed the characterization of 4 basic protein allergens: a thaumatin-like protein (osmotin) with a relative molecular mass of 27 to 29 kDa, a pectinesterase (relative molecular mass, 40 kDa), and 2 other basic proteins with relative molecular masses of 14 to 16 kDa and 43 kDa. There is no or only very weak allergen associations between pellitory and nettle pollen. Exposure to nettle pollen can be responsible of allergic symptoms, and several allergens were characterized. Unravelling the allergens of this underestimated allergy might help to improve diagnosis and care for patients, to predict cross-reactivities and design adapted specific immunotherapy. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Inelastic response of silicon to shock compression

DOE PAGES

Higginbotham, Andrew; Stubley, P. G.; Comley, A. J.; ...

2016-04-13

The elastic and inelastic response of [001] oriented silicon to laser compression has been a topic of considerable discussion for well over a decade, yet there has been little progress in understanding the basic behaviour of this apparently simple material. We present experimental x-ray diffraction data showing complex elastic strain profiles in laser compressed samples on nanosecond timescales. We also present molecular dynamics and elasticity code modelling which suggests that a pressure induced phase transition is the cause of the previously reported ‘anomalous’ elastic waves. Moreover, this interpretation allows for measurement of the kinetic timescales for transition. Lastly, this modelmore » is also discussed in the wider context of reported deformation of silicon to rapid compression in the literature.« less

Inelastic response of silicon to shock compression

PubMed Central

Higginbotham, A.; Stubley, P. G.; Comley, A. J.; Eggert, J. H.; Foster, J. M.; Kalantar, D. H.; McGonegle, D.; Patel, S.; Peacock, L. J.; Rothman, S. D.; Smith, R. F.; Suggit, M. J.; Wark, J. S.

2016-01-01

The elastic and inelastic response of [001] oriented silicon to laser compression has been a topic of considerable discussion for well over a decade, yet there has been little progress in understanding the basic behaviour of this apparently simple material. We present experimental x-ray diffraction data showing complex elastic strain profiles in laser compressed samples on nanosecond timescales. We also present molecular dynamics and elasticity code modelling which suggests that a pressure induced phase transition is the cause of the previously reported ‘anomalous’ elastic waves. Moreover, this interpretation allows for measurement of the kinetic timescales for transition. This model is also discussed in the wider context of reported deformation of silicon to rapid compression in the literature. PMID:27071341

The Use of New Technologies in Basic Education: An Approach to Profile of Indigenous Ecuadorians

ERIC Educational Resources Information Center

Stefos, Efstathios; Castellano, José Manuel; Marchán, Andrés Bonilla; Biloon, Julia Raina Sevy

2017-01-01

This article aims to define the profile of Ecuadorian indigenous students who study at different levels of basic education in Ecuador in the context of the application and use of emerging technologies in the last five years. This approach focuses on a comparative analysis between indigenous and non-indigenous students, based on the national data…

Cancer diagnostics: The journey from histomorphology to molecular profiling.

PubMed

Ahmed, Atif A; Abedalthagafi, Malak

2016-09-06

Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management.

Velocity profiles of high-excitation molecular hydrogen lines

NASA Technical Reports Server (NTRS)

Moorhouse, A.; Brand, P. W. J. L.; Geballe, T. R.; Burton, M. G.

1990-01-01

Profiles of three lines of molecular hydrogen near 2.2 microns, originating from widely spaced energy levels, have been measured at a resolution of 32 km/s at Peak 1 in the Orion molecular outflow. The three lines, 1 - 0 S(1), 2 - 1 S(1), and 3 - 2 S(3), are found to have identical profiles. This result rules out any significant contribution to the population of the higher energy levels of molecular hydrogen at Peak 1 by fluorescence, and is generally consistent with emission from multiple J-type shocks.

Real-time PCR (qPCR) primer design using free online software.

PubMed

Thornton, Brenda; Basu, Chhandak

2011-01-01

Real-time PCR (quantitative PCR or qPCR) has become the preferred method for validating results obtained from assays which measure gene expression profiles. The process uses reverse transcription polymerase chain reaction (RT-PCR), coupled with fluorescent chemistry, to measure variations in transcriptome levels between samples. The four most commonly used fluorescent chemistries are SYBR® Green dyes and TaqMan®, Molecular Beacon or Scorpion probes. SYBR® Green is very simple to use and cost efficient. As SYBR® Green dye binds to any double-stranded DNA product, its success depends greatly on proper primer design. Many types of online primer design software are available, which can be used free of charge to design desirable SYBR® Green-based qPCR primers. This laboratory exercise is intended for those who have a fundamental background in PCR. It addresses the basic fluorescent chemistries of real-time PCR, the basic rules and pitfalls of primer design, and provides a step-by-step protocol for designing SYBR® Green-based primers with free, online software. Copyright © 2010 Wiley Periodicals, Inc.

Structure-activity relationships studies on weakly basic N-arylsulfonylindoles with an antagonistic profile in the 5-HT6 receptor

NASA Astrophysics Data System (ADS)

Mella, Jaime; Villegas, Francisco; Morales-Verdejo, César; Lagos, Carlos F.; Recabarren-Gajardo, Gonzalo

2017-07-01

We recently reported a series of 39 weakly basic N-arylsulfonylindoles as novel 5-HT6 antagonists. Eight of the compounds exhibited moderate to high binding affinities, with 2-(4-(2-Methoxyphenyl)piperazin-1-yl)-1-(1-tosyl-1H-indol-3-yl)ethanol 16 showing the highest binding affinity (pKi = 7.87). Given these encouraging results and as a continuation of our research, we performed an extensive step-by-step search for the best 3D-QSAR model that allows us to rationally propose novel molecules with improved 5-HT6 affinity based on our previously reported series. A comparative molecular similarity indices analysis (CoMSIA) model built on a docking-based alignment was developed, wherein steric, electrostatic, hydrophobic and hydrogen bond properties are correlated with biological activity. The model was validated internally and externally (q2 = 0.721; r2pred = 0.938), and identified the sulfonyl and hydroxyl groups and the piperazine ring among the main regions of the molecules that can be modified to create new 5-HT6 antagonists.

Comparative genomics and transcriptional profiles of Saccharopolyspora erythraea NRRL 2338 and a classically improved erythromycin over-producing strain

PubMed Central

2012-01-01

Background The molecular mechanisms altered by the traditional mutation and screening approach during the improvement of antibiotic-producing microorganisms are still poorly understood although this information is essential to design rational strategies for industrial strain improvement. In this study, we applied comparative genomics to identify all genetic changes occurring during the development of an erythromycin overproducer obtained using the traditional mutate-and- screen method. Results Compared with the parental Saccharopolyspora erythraea NRRL 2338, the genome of the overproducing strain presents 117 deletion, 78 insertion and 12 transposition sites, with 71 insertion/deletion sites mapping within coding sequences (CDSs) and generating frame-shift mutations. Single nucleotide variations are present in 144 CDSs. Overall, the genomic variations affect 227 proteins of the overproducing strain and a considerable number of mutations alter genes of key enzymes in the central carbon and nitrogen metabolism and in the biosynthesis of secondary metabolites, resulting in the redirection of common precursors toward erythromycin biosynthesis. Interestingly, several mutations inactivate genes coding for proteins that play fundamental roles in basic transcription and translation machineries including the transcription anti-termination factor NusB and the transcription elongation factor Efp. These mutations, along with those affecting genes coding for pleiotropic or pathway-specific regulators, affect global expression profile as demonstrated by a comparative analysis of the parental and overproducer expression profiles. Genomic data, finally, suggest that the mutate-and-screen process might have been accelerated by mutations in DNA repair genes. Conclusions This study helps to clarify the mechanisms underlying antibiotic overproduction providing valuable information about new possible molecular targets for rationale strain improvement. PMID:22401291

MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

PubMed

Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

2017-03-15

Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of reference and identity-defining genes in human mesenchymal stem cells cultured under unrelated fetal bovine serum batches for basic science and clinical application.

PubMed

Banfi, Federica; Colombini, Alessandra; Perucca Orfei, Carlotta; Parazzi, Valentina; Ragni, Enrico

2018-05-26

The molecular profile of human mesenchymal stem cells (MSCs) have emerged as a key factor in defining their identity. Nevertheless, the effect of fetal bovine serum (FBS) batches or origin on MSC molecular signature has been neglected. In this frame, chemical fingerprint of FBS batches from unrelated countries showed strong correlation between chemical composition and country of origin. Thus, the aim of this study was to evaluate in stem cells isolated from bone marrow (BMMSCs) and umbilical cord-blood (CBMSCs) the effects of independently collected FBS batches on both twelve commonly used reference genes (RGs) and a selected panel of thirty-eight genes crucial for MSC definition in both research and clinical settings. Gene expression stability was estimated comparing the outcomes of two applets: geNorm and NormFinder. The bioinformatics analysis emphasized that, in a panorama of general balance, few RG candidates (YWHAZ/UBC for BMMSCs, RPLP0/EF1A for CBMSCs and EF1A/TBP for both MSCs scored together) showed superior stability. In addition, a wider study on genes involved in differentiation/proliferation/stemness processes, often used to define MSC potency, showed that these genes exhibited no major transcriptional modulation after treatment with different FBS, and allowed the identification of genes strongly discriminating between BM- and CBMSC populations. Therefore, in conclusion, FBS origin does not dramatically impact the general molecular profile of MSCs, although we could identify validated candidates able to allow more reliable comparison of data regarding MSC identity and potency and obtained by research laboratories and clinical manufacturers using different sera.

Molecular profiling of angiogenesis in hypericin mediated photodynamic therapy

PubMed Central

Bhuvaneswari, Ramaswamy; Gan, Yik Y; Lucky, Sasidharan S; Chin, William WL; Ali, Seyed M; Soo, Khee C; Olivo, Malini

2008-01-01

Background Photodynamic therapy (PDT) involves the administration of a tumor-localizing photosensitizing drug, which is activated by light of specific wavelength in the presence of molecular oxygen thus generating reactive oxygen species that is toxic to the tumor cells. PDT selectively destroys photosensitized tissue leading to various cellular and molecular responses. The present study was designed to examine the angiogenic responses at short (0.5 h) and long (6 h) drug light interval (DLI) hypericin-PDT (HY-PDT) treatment at 24 h and 30 days post treatment in a human bladder carcinoma xenograft model. As short DLI targets tumor vasculature and longer DLI induces greater cellular damage, we hypothesized a differential effect of these treatments on the expression of angiogenic factors. Results Immunohistochemistry (IHC) results showed minimal CD31 stained endothelium at 24 h post short DLI PDT indicating extensive vascular damage. Angiogenic proteins such as vascular endothelial growth factor (VEGF), tumor necrosis growth factor-α (TNF-α), interferon-α (IFN-α) and basic fibroblast growth factor (bFGF) were expressed to a greater extent in cellular targeting long DLI PDT compared to vascular mediated short DLI PDT. Gene expression profiling for angiogenesis pathway demonstrated downregulation of adhesion molecules – cadherin 5, collagen alpha 1 and 3 at 24 h post treatment. Hepatocyte growth factor (HGF) and Ephrin-A3 (EFNA3) were upregulated in all treatment groups suggesting a possible activation of c-Met and Ephrin-Eph signaling pathways. Conclusion In conclusion, long DLI HY-PDT induces upregulation of angiogenic proteins. Differential expression of genes involved in the angiogenesis pathway was observed in the various groups treated with HY-PDT. PMID:18549507

Multiscale modeling of a rectifying bipolar nanopore: explicit-water versus implicit-water simulations.

PubMed

Ható, Zoltán; Valiskó, Mónika; Kristóf, Tamás; Gillespie, Dirk; Boda, Dezsö

2017-07-21

In a multiscale modeling approach, we present computer simulation results for a rectifying bipolar nanopore at two modeling levels. In an all-atom model, we use explicit water to simulate ion transport directly with the molecular dynamics technique. In a reduced model, we use implicit water and apply the Local Equilibrium Monte Carlo method together with the Nernst-Planck transport equation. This hybrid method makes the fast calculation of ion transport possible at the price of lost details. We show that the implicit-water model is an appropriate representation of the explicit-water model when we look at the system at the device (i.e., input vs. output) level. The two models produce qualitatively similar behavior of the electrical current for different voltages and model parameters. Looking at the details of concentration and potential profiles, we find profound differences between the two models. These differences, however, do not influence the basic behavior of the model as a device because they do not influence the z-dependence of the concentration profiles which are the main determinants of current. These results then address an old paradox: how do reduced models, whose assumptions should break down in a nanoscale device, predict experimental data? Our simulations show that reduced models can still capture the overall device physics correctly, even though they get some important aspects of the molecular-scale physics quite wrong; reduced models work because they include the physics that is necessary from the point of view of device function. Therefore, reduced models can suffice for general device understanding and device design, but more detailed models might be needed for molecular level understanding.

Oxygen regulates molecular mechanisms of cancer progression and metastasis.

PubMed

Gupta, Kartik; Madan, Esha; Sayyid, Muzzammil; Arias-Pulido, Hugo; Moreno, Eduardo; Kuppusamy, Periannan; Gogna, Rajan

2014-03-01

Oxygen is the basic molecule which supports life and it truly is "god's gift to life." Despite its immense importance, research on "oxygen biology" has never received the light of the day and has been limited to physiological and biochemical studies. It seems that in modern day biology, oxygen research is summarized in one word "hypoxia." Scientists have focused on hypoxia-induced transcriptomics and molecular-cellular alterations exclusively in disease models. Interestingly, the potential of oxygen to control the basic principles of biology like homeostatic maintenance, transcription, replication, and protein folding among many others, at the molecular level, has been completely ignored. Here, we present a perspective on the crucial role played by oxygen in regulation of basic biological phenomena. Our conclusion highlights the importance of establishing novel research areas like oxygen biology, as there is great potential in this field for basic science discoveries and clinical benefits to the society.

Unmasking molecular profiles of bladder cancer.

PubMed

Piao, Xuan-Mei; Byun, Young Joon; Kim, Wun-Jae; Kim, Jayoung

2018-03-01

Precision medicine is designed to tailor treatments for individual patients by factoring in each person's specific biology and mechanism of disease. This paradigm shifted from a "one size fits all" approach to "personalized and precision care" requires multiple layers of molecular profiling of biomarkers for accurate diagnosis and prediction of treatment responses. Intensive studies are also being performed to understand the complex and dynamic molecular profiles of bladder cancer. These efforts involve looking bladder cancer mechanism at the multiple levels of the genome, epigenome, transcriptome, proteome, lipidome, metabolome etc. The aim of this short review is to outline the current technologies being used to investigate molecular profiles and discuss biomarker candidates that have been investigated as possible diagnostic and prognostic indicators of bladder cancer.

Quantitative structure-retention relationship studies using immobilized artificial membrane chromatography I: amended linear solvation energy relationships with the introduction of a molecular electronic factor.

PubMed

Li, Jie; Sun, Jin; Cui, Shengmiao; He, Zhonggui

2006-11-03

Linear solvation energy relationships (LSERs) amended by the introduction of a molecular electronic factor were employed to establish quantitative structure-retention relationships using immobilized artificial membrane (IAM) chromatography, in particular ionizable solutes. The chromatographic indices, log k(IAM), were determined by HPLC on an IAM.PC.DD2 column for 53 structurally diverse compounds, including neutral, acidic and basic compounds. Unlike neutral compounds, the IAM chromatographic retention of ionizable compounds was affected by their molecular charge state. When the mean net charge per molecule (delta) was introduced into the amended LSER as the sixth variable, the LSER regression coefficient was significantly improved for the test set including ionizable solutes. The delta coefficients of acidic and basic compounds were quite different indicating that the molecular electronic factor had a markedly different impact on the retention of acidic and basic compounds on IAM column. Ionization of acidic compounds containing a carboxylic group tended to impair their retention on IAM, while the ionization of basic compounds did not have such a marked effect. In addition, the extra-interaction with the polar head of phospholipids might cause a certain change in the retention of basic compounds. A comparison of calculated and experimental retention indices suggested that the semi-empirical LSER amended by the addition of a molecular electronic factor was able to reproduce adequately the experimental retention factors of the structurally diverse solutes investigated.

Translational bioinformatics: linking the molecular world to the clinical world.

PubMed

Altman, R B

2012-06-01

Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care.

Utilization of Gastrointestinal Simulator, an in Vivo Predictive Dissolution Methodology, Coupled with Computational Approach To Forecast Oral Absorption of Dipyridamole.

PubMed

Matsui, Kazuki; Tsume, Yasuhiro; Takeuchi, Susumu; Searls, Amanda; Amidon, Gordon L

2017-04-03

Weakly basic drugs exhibit a pH-dependent dissolution profile in the gastrointestinal (GI) tract, which makes it difficult to predict their oral absorption profile. The aim of this study was to investigate the utility of the gastrointestinal simulator (GIS), a novel in vivo predictive dissolution (iPD) methodology, in predicting the in vivo behavior of the weakly basic drug dipyridamole when coupled with in silico analysis. The GIS is a multicompartmental dissolution apparatus, which represents physiological gastric emptying in the fasted state. Kinetic parameters for drug dissolution and precipitation were optimized by fitting a curve to the dissolved drug amount-time profiles in the United States Pharmacopeia apparatus II and GIS. Optimized parameters were incorporated into mathematical equations to describe the mass transport kinetics of dipyridamole in the GI tract. By using this in silico model, intraluminal drug concentration-time profile was simulated. The predicted profile of dipyridamole in the duodenal compartment adequately captured observed data. In addition, the plasma concentration-time profile was also predicted using pharmacokinetic parameters following intravenous administration. On the basis of the comparison with observed data, the in silico approach coupled with the GIS successfully predicted in vivo pharmacokinetic profiles. Although further investigations are still required to generalize, these results indicated that incorporating GIS data into mathematical equations improves the predictability of in vivo behavior of weakly basic drugs like dipyridamole.

Basic emotion profiles in healthy, chronic pain, depressed and PTSD individuals.

PubMed

Finucane, Anne M; Dima, Alexandra; Ferreira, Nuno; Halvorsen, Marianne

2012-01-01

To compare self-reports of five basic emotions across four samples: healthy, chronic pain, depressed and post-traumatic stress disorder (PTSD), and to investigate the extent to which basic emotion reports discriminate between individuals in healthy or clinical groups. In total, 439 participants took part in this study: healthy (n = 131), chronic pain (n = 220), depressed (n = 24) and PTSD (n = 64). The participants completed the trait version of the Basic Emotion Scale. Basic emotion profiles were compared both within each group and between the healthy group and each of the three other groups. Discriminant analysis was used to assess the extent to which basic emotions can be used to classify the participants as belonging to the healthy group or one of the clinical groups. In the healthy group, happiness was experienced more than any other basic emotion. This was not found in the clinical groups. In comparison to the healthy participants, the chronic pain group experienced more fear, anger and sadness, the depressed group reported more sadness and the PTSD group experienced all of the negative emotions more frequently. Discriminant analysis revealed that happiness was the most important variable in determining whether an individual belonged to the healthy group or one of the clinical groups. Anger was found to further discriminate between depressed and chronic pain individuals. The findings demonstrate that basic emotion profile analysis can provide a useful foundation for the exploration of emotional experience both within and between healthy and clinical groups.  Copyright © 2011 John Wiley & Sons, Ltd.

Technical aspects and recommendations for single-cell qPCR.

PubMed

Ståhlberg, Anders; Kubista, Mikael

2018-02-01

Single cells are basic physiological and biological units that can function individually as well as in groups in tissues and organs. It is central to identify, characterize and profile single cells at molecular level to be able to distinguish different kinds, to understand their functions and determine how they interact with each other. During the last decade several technologies for single-cell profiling have been developed and used in various applications, revealing many novel findings. Quantitative PCR (qPCR) is one of the most developed methods for single-cell profiling that can be used to interrogate several analytes, including DNA, RNA and protein. Single-cell qPCR has the potential to become routine methodology but the technique is still challenging, as it involves several experimental steps and few molecules are handled. Here, we discuss technical aspects and provide recommendation for single-cell qPCR analysis. The workflow includes experimental design, sample preparation, single-cell collection, direct lysis, reverse transcription, preamplification, qPCR and data analysis. Detailed reporting and sharing of experimental details and data will promote further development and make validation studies possible. Efforts aiming to standardize single-cell qPCR open up means to move single-cell analysis from specialized research settings to standard research laboratories. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-resolution structure of Drosophila translin

PubMed Central

Kumar, Vinay; Gupta, Gagan D.

2012-01-01

Crystals of native Drosophila melanogaster translin diffracted to 7 Å resolution. Reductive methylation of the protein improved crystal quality. The native and methylated proteins showed similar profiles in size-exclusion chromatography analyses but the methylated protein displayed reduced DNA-binding activity. Crystals of the methylated protein diffracted to 4.2 Å resolution at BM14 of the ESRF synchrotron. Crystals with 49% solvent content belonged to monoclinic space group P21 with eight protomers in the asymmetric unit. Only 2% of low-resolution structures with similar low percentage solvent content were found in the PDB. The crystal structure, solved by molecular replacement method, refined to Rwork (Rfree) of 0.24 (0.29) with excellent stereochemistry. The crystal structure clearly shows that drosophila protein exists as an octamer, and not as a decamer as expected from gel-filtration elution profiles. The similar octameric quaternary fold in translin orthologs and in translin–TRAX complexes suggests an up-down dimer as the basic structural subunit of translin-like proteins. The drosophila oligomer displays asymmetric assembly and increased radius of gyration that accounts for the observed differences between the elution profiles of human and drosophila proteins on gel-filtration columns. This study demonstrates clearly that low-resolution X-ray structure can be useful in understanding complex biological oligomers. PMID:23650579

NCCN Oncology Research Program's Investigator Steering Committee and NCCN Best Practices Committee Molecular Profiling Surveys.

PubMed

Kurzrock, Razelle; Colevas, A Dimitrios; Olszanski, Anthony; Akerley, Wallace; Arteaga, Carlos L; Carson, William E; Clark, Jeffrey W; DiPersio, John F; Ettinger, David S; Morgan, Robert J; Schwartzberg, Lee S; Venook, Alan P; Gocke, Christopher D; Tait, Jonathan; Stewart, F Marc

2015-11-01

With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, "molecular profiling/diagnostics" was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care. Copyright © 2015 by the National Comprehensive Cancer Network.

UGV Control Interoperability Profile (IOP), Version 0

DTIC Science & Technology

2011-12-21

task or function associated with the ID (e.g. “select asset gear” and “switch between local and zulu time display”). Category Provides a high...CTRL- Basic Status-2 view Zulu date and time in Date-Time-Group (DTG) format Basic Status S SWP Icon (text) CTRL- Basic Status-3 switch...between local and zulu time display Basic Status C SW1 CTRL- Basic Status-4 view unique identifier/call sign for each asset Basic Status S

Managing the genomic revolution in cancer diagnostics.

PubMed

Nguyen, Doreen; Gocke, Christopher D

2017-08-01

Molecular tumor profiling is now a routine part of patient care, revealing targetable genomic alterations and molecularly distinct tumor subtypes with therapeutic and prognostic implications. The widespread adoption of next-generation sequencing technologies has greatly facilitated clinical implementation of genomic data and opened the door for high-throughput multigene-targeted sequencing. Herein, we discuss the variability of cancer genetic profiling currently offered by clinical laboratories, the challenges of applying rapidly evolving medical knowledge to individual patients, and the need for more standardized population-based molecular profiling.

Mixed convective/dynamic roll vortices and their effects on initial wind and temperature profiles

NASA Technical Reports Server (NTRS)

Haack, Tracy; Shirer, Hampton N.

1991-01-01

The onset and development of both dynamically and convectively forced boundary layer rolls are studied with linear and nonlinear analyses of a truncated spectral model of shallow Boussinesq flow. Emphasis is given here on the energetics of the dominant roll modes, on the magnitudes of the roll-induced modifications of the initial basic state wind and temperature profiles, and on the sensitivity of the linear stability results to the use of modified profiles as basic states. It is demonstrated that the roll circulations can produce substantial changes to the cross-roll component of the initial wind profile and that significant changes in orientation angle estimates can result from use of a roll-modified profile in the stability analysis. These results demonstrate that roll contributions must be removed from observed background wind profiles before using them to investigate the mechanisms underlying actual secondary flows in the boundary layer. The model is developed quite generally to accept arbitrary basic state wind profiles as dynamic forcing. An Ekman profile is chosen here merely to provide a means for easy comparison with other theoretical boundary layer studies; the ultimate application of the model is to study observed boundary layer profiles. Results of the analytic stability analysis are validated by comparing them with results from a larger linear model. For an appropriate Ekman depth, a complete set of transition curves is given in forcing parameter space for roll modes driven both thermally and dynamically. Preferred orientation angles, horizontal wavelengths and propagation frequencies, as well as energetics and wind profile modifications, are all shown to agree rather well with results from studies on Ekman layers as well as with studies on near-neutral and convective atmospheric boundary layers.

The daily timing of gene expression and physiology in mammals

PubMed Central

Schibler, Ueli

2007-01-01

Mammalian behavior and physiology undergo daily rhythms that are coordinated by an endogenous circadian timing system. This system has a hierarchical structure, in that a master pacemaker, residing in the suprachiasmatic nucleus of the ventral hypothalamus, synchronizes peripheral oscillators in virtually all body cells. While the basic molecular mechanisms generating the daily rhythms are similar in aIl cells, most clock out-puts are cell-specific. This conclusion is based on genomewide transcriptome profiling studies in several tissues that have revealed hundreds of rhythmically expressed genes. Cyclic gene expression in the various organs governs overt rhythms in behavior and physiology, encompassing sleep-wake cycles, metabolism, xenobiotic detoxification, and cellularproliferation. As a consequence, chronic perturbation of this temporal organization may lead to increased morbidity and reduced lifespan. PMID:17969863

Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know†

PubMed Central

Opitz, Isabelle; Bueno, Raphael; Lim, Eric; Pass, Harvey; Pastorino, Ugo; Boeri, Mattia; Rocco, Gaetano

2014-01-01

Today, molecular-profile-directed therapy is a guiding principle of modern thoracic oncology. The knowledge of new biomolecular technology applied to the diagnosis, prognosis, and treatment of lung cancer and mesothelioma should be part of the 21st century thoracic surgeons' professional competence. The European Society of Thoracic Surgeons (ESTS) Biology Club aims at providing a comprehensive insight into the basic biology of the diseases we are treating. During the 2013 ESTS Annual Meeting, different experts of the field presented the current knowledge about diagnostic and prognostic biomarkers in malignant pleural mesothelioma including new perspectives as well as the role and potential application of microRNA and genomic sequencing for lung cancer, which are summarized in the present article. PMID:24623168

Investigating the Fundamentals of Molecular Depth Profiling Using Strong-field Photoionization of Sputtered Neutrals

PubMed Central

Willingham, D.; Brenes, D. A.; Winograd, N.; Wucher, A.

2010-01-01

Molecular depth profiles of model organic thin films were performed using a 40 keV C60+ cluster ion source in concert with TOF-SIMS. Strong-field photoionization of intact neutral molecules sputtered by 40 keV C60+ primary ions was used to analyze changes in the chemical environment of the guanine thin films as a function of ion fluence. Direct comparison of the secondary ion and neutral components of the molecular depth profiles yields valuable information about chemical damage accumulation as well as changes in the molecular ionization probability. An analytical protocol based on the erosion dynamics model is developed and evaluated using guanine and trehalose molecular secondary ion signals with and without comparable laser photoionization data. PMID:26269660

Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

PubMed

Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

2017-11-29

Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

Vascular biology: cellular and molecular profiling.

PubMed

Baird, Alison E; Wright, Violet L

2006-02-01

Our understanding of the mechanisms underlying cerebrovascular atherosclerosis has improved in recent years, but significant gaps remain. New insights into the vascular biological processes that result in ischemic stroke may come from cellular and molecular profiling studies of the peripheral blood. In recent cellular profiling studies, increased levels of a proinflammatory T-cell subset (CD4 (+)CD28 (-)) have been associated with stroke recurrence and death. Expansion of this T-cell subset may occur after ischemic stroke and be a pathogenic mechanism leading to recurrent stroke and death. Increases in certain phenotypes of endothelial cell microparticles have been found in stroke patients relative to controls, possibly indicating a state of increased vascular risk. Molecular profiling approaches include gene expression profiling and proteomic methods that permit large-scale analyses of the transcriptome and the proteome, respectively. Ultimately panels of genes and proteins may be identified that are predictive of stroke risk. Cellular and molecular profiling studies of the peripheral blood and of atherosclerotic plaques may also pave the way for the development of therapeutic agents for primary and secondary stroke prevention.

Centro de Biologia Molecular "Severo Ochoa": a center for basic research into Alzheimer's disease.

PubMed

Avila, Jesus; Hernandez, Felix; Wandosell, Francisco; Lucas, Jose J; Esteban, Jose A; Ledesma, M Dolores; Bullido, Maria J

2010-01-01

One important aspect of studies carried out at the Center for Molecular Biology "Severo Ochoa" is focused on basic aspects of Alzheimer's disease, mainly the search for suitable therapeutic targets for this disorder. Several groups at the Center are involved in these studies, and, in this spotlight, the work they are carrying out will be described.

Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

PubMed Central

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

2013-01-01

Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

Profiles of 1975-76 Supplemental Basic Grant Applicants.

ERIC Educational Resources Information Center

Walters, Pamela Barnhouse

The nature and extent of misreporting by applicants for the Basic Educational Opportunity Grant program was investigated. Types of potential program abuse were assessed, along with the accuracy of income estimates that students make on Supplemental Basic Grant applications, which are the basis for determining a student's eligibility. Attention was…

Use of a novel cation-exchange restricted-access material for automated sample clean-up prior to the determination of basic drugs in plasma by liquid chromatography.

PubMed

Chiap, P; Rbeida, O; Christiaens, B; Hubert, Ph; Lubda, D; Boos, K S; Crommen, J

2002-10-25

A new kind of silica-based restricted-access material (RAM) has been tested in pre-columns for the on-line solid-phase extraction (SPE) of basic drugs from directly injected plasma samples before their quantitative analysis by reversed-phase liquid chromatography (LC), using the column switching technique. The outer surface of the porous RAM particlescontains hydrophilic diol groups while sulphonic acid groups are bound to the internal surface, which gives the sorbent the properties of a strong cation exchanger towards low molecular mass compounds. Macromolecules such as proteins have no access to the internal surface of the pre-column due to their exclusion from the pores and are then flushed directly out. The retention capability of this novel packing material has been tested for some hydrophilic basic drugs, such as atropine, fenoterol, ipratropium, procaine, sotalol and terbutaline, used as model compounds. The influence of the composition of the washing liquid on the retention of the analytes in the pre-column has been investigated. The elution profiles of the different compounds and the plasma matrix as well as the time needed for the transfer of the analytes from the pre-column to the analytical column were determined in order to deduce the most suitable conditions for the clean-up step and develop on-line methods for the LC determination of these compounds in plasma. The cationic exchange sorbent was also compared to another RAM, namely RP-18 ADS (alkyl diol silica) sorbent with respect to retention capability towards basic analytes.

Cocoa content influences chocolate molecular profile investigated by MALDI-TOF mass spectrometry.

PubMed

Bonatto, Cínthia C; Silva, Luciano P

2015-06-01

Chocolate authentication is a key aspect of quality control and safety. Matrix-assisted laser desorption ionization time-of flight (MALDI-TOF) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of cells, tissues, and even food. The present study evaluated if MALDI-TOF MS analysis on low molecular mass profile may classify chocolate samples according to the cocoa content. The molecular profiles of seven processed commercial chocolate samples were compared by using MALDI-TOF MS. Some ions detected exclusively in chocolate samples corresponded to the metabolites of cocoa or other constituents. This method showed the presence of three distinct clusters according to confectionery and sensorial features of the chocolates and was used to establish a mass spectra database. Also, novel chocolate samples were evaluated in order to check the validity of the method and to challenge the database created with the mass spectra of the primary samples. Thus, the method was shown to be reliable for clustering unknown samples into the main chocolate categories. Simple sample preparation of the MALDI-TOF MS approach described will allow the surveillance and monitoring of constituents during the molecular profiling of chocolates. © 2014 Society of Chemical Industry.

Relationship of carbohydrate molecular spectroscopic features in combined feeds to carbohydrate utilization and availability in ruminants

NASA Astrophysics Data System (ADS)

Zhang, Xuewei; Yu, Peiqiang

To date, there is no study on the relationship between carbohydrate (CHO) molecular structures and nutrient availability of combined feeds in ruminants. The objective of this study was to use molecular spectroscopy to reveal the relationship between CHO molecular spectral profiles (in terms of functional groups (biomolecular, biopolymer) spectral peak area and height intensity) and CHO chemical profiles, CHO subfractions, energy values, and CHO rumen degradation kinetics of combined feeds of hulless barley with pure wheat dried distillers grains with solubles (DDGS) at five different combination ratios (hulless barley to pure wheat DDGS: 100:0, 75:25, 50:50, 25:75, 0:100). The molecular spectroscopic parameters assessed included: lignin biopolymer molecular spectra profile (peak area and height, region and baseline: ca. 1539-1504 cm-1); structural carbohydrate (STCHO, peaks area region and baseline: ca. 1485-1186 cm-1) mainly associated with hemi- and cellulosic compounds; cellulosic materials peak area (centered at ca. 1240 cm-1 with region and baseline: ca. 1272-1186 cm-1); total carbohydrate (CHO, peaks area region and baseline: ca. 1186-946 cm-1). The results showed that the functional groups (biomolecular, biopolymer) in the combined feeds are sensitive to the changes of carbohydrate chemical and nutrient profiles. The changes of the CHO molecular spectroscopic features in the combined feeds were highly correlated with CHO chemical profiles, CHO subfractions, in situ CHO rumen degradation kinetics and fermentable organic matter supply. Further study is needed to investigate possibility of using CHO molecular spectral features as a predictor to estimate nutrient availability in combined feeds for animals and quantify their relationship.

[The development of molecular human genetics and its significance for perspectives of modern medicine].

PubMed

Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

1989-01-01

The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

The Basic/Helix-Loop-Helix Protein Family in Gossypium: Reference Genes and Their Evolution during Tetraploidization

PubMed Central

Yan, Qian; Liu, Hou-Sheng; Yao, Dan; Li, Xin; Chen, Han; Dou, Yang; Wang, Yi; Pei, Yan; Xiao, Yue-Hua

2015-01-01

Basic/helix-loop-helix (bHLH) proteins comprise one of the largest transcription factor families and play important roles in diverse cellular and molecular processes. Comprehensive analyses of the composition and evolution of the bHLH family in cotton are essential to elucidate their functions and the molecular basis of cotton development. By searching bHLH homologous genes in sequenced diploid cotton genomes (Gossypium raimondii and G. arboreum), a set of cotton bHLH reference genes containing 289 paralogs were identified and named as GobHLH001-289. Based on their phylogenetic relationships, these cotton bHLH proteins were clustered into 27 subfamilies. Compared to those in Arabidopsis and cacao, cotton bHLH proteins generally increased in number, but unevenly in different subfamilies. To further uncover evolutionary changes of bHLH genes during tetraploidization of cotton, all genes of S5a and S5b subfamilies in upland cotton and its diploid progenitors were cloned and compared, and their transcript profiles were determined in upland cotton. A total of 10 genes of S5a and S5b subfamilies (doubled from A- and D-genome progenitors) maintained in tetraploid cottons. The major sequence changes in upland cotton included a 15-bp in-frame deletion in GhbHLH130D and a long terminal repeat retrotransposon inserted in GhbHLH062A, which eliminated GhbHLH062A expression in various tissues. The S5a and S5b bHLH genes of A and D genomes (except GobHLH062) showed similar transcription patterns in various tissues including roots, stems, leaves, petals, ovules, and fibers, while the A- and D-genome genes of GobHLH110 and GobHLH130 displayed clearly different transcript profiles during fiber development. In total, this study represented a genome-wide analysis of cotton bHLH family, and revealed significant changes in sequence and expression of these genes in tetraploid cottons, which paved the way for further functional analyses of bHLH genes in the cotton genus. PMID:25992947

The Basic/Helix-Loop-Helix Protein Family in Gossypium: Reference Genes and Their Evolution during Tetraploidization.

PubMed

Yan, Qian; Liu, Hou-Sheng; Yao, Dan; Li, Xin; Chen, Han; Dou, Yang; Wang, Yi; Pei, Yan; Xiao, Yue-Hua

2015-01-01

Basic/helix-loop-helix (bHLH) proteins comprise one of the largest transcription factor families and play important roles in diverse cellular and molecular processes. Comprehensive analyses of the composition and evolution of the bHLH family in cotton are essential to elucidate their functions and the molecular basis of cotton development. By searching bHLH homologous genes in sequenced diploid cotton genomes (Gossypium raimondii and G. arboreum), a set of cotton bHLH reference genes containing 289 paralogs were identified and named as GobHLH001-289. Based on their phylogenetic relationships, these cotton bHLH proteins were clustered into 27 subfamilies. Compared to those in Arabidopsis and cacao, cotton bHLH proteins generally increased in number, but unevenly in different subfamilies. To further uncover evolutionary changes of bHLH genes during tetraploidization of cotton, all genes of S5a and S5b subfamilies in upland cotton and its diploid progenitors were cloned and compared, and their transcript profiles were determined in upland cotton. A total of 10 genes of S5a and S5b subfamilies (doubled from A- and D-genome progenitors) maintained in tetraploid cottons. The major sequence changes in upland cotton included a 15-bp in-frame deletion in GhbHLH130D and a long terminal repeat retrotransposon inserted in GhbHLH062A, which eliminated GhbHLH062A expression in various tissues. The S5a and S5b bHLH genes of A and D genomes (except GobHLH062) showed similar transcription patterns in various tissues including roots, stems, leaves, petals, ovules, and fibers, while the A- and D-genome genes of GobHLH110 and GobHLH130 displayed clearly different transcript profiles during fiber development. In total, this study represented a genome-wide analysis of cotton bHLH family, and revealed significant changes in sequence and expression of these genes in tetraploid cottons, which paved the way for further functional analyses of bHLH genes in the cotton genus.

Investigating Molecular Structures of Bio-Fuel and Bio-Oil Seeds as Predictors To Estimate Protein Bioavailability for Ruminants by Advanced Nondestructive Vibrational Molecular Spectroscopy.

PubMed

Ban, Yajing; L Prates, Luciana; Yu, Peiqiang

2017-10-18

This study was conducted to (1) determine protein and carbohydrate molecular structure profiles and (2) quantify the relationship between structural features and protein bioavailability of newly developed carinata and canola seeds for dairy cows by using Fourier transform infrared molecular spectroscopy. Results showed similarity in protein structural makeup within the entire protein structural region between carinata and canola seeds. The highest area ratios related to structural CHO, total CHO, and cellulosic compounds were obtained for carinata seeds. Carinata and canola seeds showed similar carbohydrate and protein molecular structures by multivariate analyses. Carbohydrate molecular structure profiles were highly correlated to protein rumen degradation and intestinal digestion characteristics. In conclusion, the molecular spectroscopy can detect inherent structural characteristics in carinata and canola seeds in which carbohydrate-relative structural features are related to protein metabolism and utilization. Protein and carbohydrate spectral profiles could be used as predictors of rumen protein bioavailability in cows.

Current concepts for the combined treatment modality of ionizing radiation with anticancer agents.

PubMed

Oehler, Christoph; Dickinson, Daniel J; Broggini-Tenzer, Angela; Hofstetter, Barbara; Hollenstein, Andreas; Riesterer, Oliver; Vuong, Van; Pruschy, Martin

2007-01-01

In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's.

A Profile Examination System for Physician Extenders and a Method for Curricular Prescription. Final Report.

ERIC Educational Resources Information Center

Smull, Ned W.; And Others

The basic purposes of the Profile Examination for Physician Extenders (PEPE) project included: (1) development of a computerized test item bank from which Profile Examinations could be generated, (2) review and analysis of curricula for the allied health groups, and (3) assessment of the reliability and validity of the Profile Examinations. The…

Introducing basic molecular biology to Turkish rural and urban primary school children via hands-on PCR and gel electrophoresis activities.

PubMed

Selli, Cigdem; Yıldırım, Gokce; Kaymak, Aysegul; Karacicek, Bilge; Ogut, Deniz; Gungor, Turkan; Erem, Erdem; Ege, Mehmet; Bümen, Nilay; Tosun, Metiner

2014-01-01

This study includes the results of a 2-day education project titled "Molecular Biology Laboratory Summer School, MoBiLYO." The project was held at a University Research Center by scientists from Department of Pharmacology and graduate students. The project was composed of introductory lectures, model construction, DNA isolation, polymerase chain reaction (PCR), and gel electrophoresis. The participants were 13-year-old eighth-graders attending primary schools affiliated with Ministry of National Education in urban and rural areas of Izmir, Turkey. The purpose of this study was to introduce basic molecular biology concepts through individually performed experiments such as PCR and gel electrophoresis integrated with creative drama. The students were assessed at the beginning and the end of each project day via mini-tests, experimental and presentation skills evaluation forms. Data showed that students' knowledge about DNA structure and basic molecular biology techniques significantly increased. On the basis of experimental and presentational skills, there was no significant difference between kids from urban and rural schools or between public and boarding public schools, whereas the average score of girls was significantly higher than that of boys. In conclusion, individually performed experiments integrated with creative drama significantly increased students' perception of complex experimental procedures on basic molecular biology concepts. Data suggests that integration of these concepts into the science and technology curriculum of Turkish primary education may support the recruitment of future scientists who can handle rapidly developing genomic techniques that will affect our everyday life. © 2014 by The International Union of Biochemistry and Molecular Biology.

RED: a set of molecular descriptors based on Renyi entropy.

PubMed

Delgado-Soler, Laura; Toral, Raul; Tomás, M Santos; Rubio-Martinez, Jaime

2009-11-01

New molecular descriptors, RED (Renyi entropy descriptors), based on the generalized entropies introduced by Renyi are presented. Topological descriptors based on molecular features have proven to be useful for describing molecular profiles. Renyi entropy is used as a variability measure to contract a feature-pair distribution composing the descriptor vector. The performance of RED descriptors was tested for the analysis of different sets of molecular distances, virtual screening, and pharmacological profiling. A free parameter of the Renyi entropy has been optimized for all the considered applications.

The basic helix-loop-helix transcription factor Nex-1/Math-2 promotes neuronal survival of PC12 cells by modulating the dynamic expression of anti-apoptotic and cell cycle regulators

PubMed Central

Uittenbogaard, Martine; Chiaramello, Anne

2006-01-01

The basic helix-loop-helix transcription factor Nex1/Math-2 belongs to the NeuroD subfamily, which plays a critical role during neuronal differentiation and maintenance of the differentiated state. Previously, we demonstrated that Nex1 is a key regulatory component of the nerve growth factor (NGF) pathway. Further supporting this hypothesis, this study shows that Nex1 has survival-inducing properties similar to NGF, as Nex1-overexpressing PC12 cells survive in the absence of trophic factors. We dissected the molecular mechanism by which Nex1 confers neuroprotection upon serum removal and found that constitutive expression of Nex1 maintained the expression of specific G1 phase cyclin-dependent kinase inhibitors and concomitantly induced a dynamic expression profile of key anti-apoptotic regulators. This study provides the first evidence of the underlying mechanism by which a member of the NeuroD-subfamily promotes an active anti-apoptotic program essential to the survival of neurons. Our results suggest that the survival program may be viewed as an integral component of the intrinsic programming of the differ entiated state. PMID:15659228

The emergence of molecular profiling and omics techniques in seagrass biology; furthering our understanding of seagrasses.

PubMed

Davey, Peter A; Pernice, Mathieu; Sablok, Gaurav; Larkum, Anthony; Lee, Huey Tyng; Golicz, Agnieszka; Edwards, David; Dolferus, Rudy; Ralph, Peter

2016-09-01

Seagrass meadows are disappearing at alarming rates as a result of increasing coastal development and climate change. The emergence of omics and molecular profiling techniques in seagrass research is timely, providing a new opportunity to address such global issues. Whilst these applications have transformed terrestrial plant research, they have only emerged in seagrass research within the past decade; In this time frame we have observed a significant increase in the number of publications in this nascent field, and as of this year the first genome of a seagrass species has been sequenced. In this review, we focus on the development of omics and molecular profiling and the utilization of molecular markers in the field of seagrass biology. We highlight the advances, merits and pitfalls associated with such technology, and importantly we identify and address the knowledge gaps, which to this day prevent us from understanding seagrasses in a holistic manner. By utilizing the powers of omics and molecular profiling technologies in integrated strategies, we will gain a better understanding of how these unique plants function at the molecular level and how they respond to on-going disturbance and climate change events.

The Graduate Training Programme "Molecular Imaging for the Analysis of Gene and Protein Expression": A Case Study with an Insight into the Participation of Universities of Applied Sciences

ERIC Educational Resources Information Center

Hafner, Mathias

2008-01-01

Cell biology and molecular imaging technologies have made enormous progress in basic research. However, the transfer of this knowledge to the pharmaceutical drug discovery process, or even therapeutic improvements for disorders such as neuronal diseases, is still in its infancy. This transfer needs scientists who can integrate basic research with…

Bibliometric analysis of original molecular biology research in anaesthesia.

PubMed

Schreiber, K; Girard, T; Kindler, C H

2004-10-01

Molecular biology has expanded the horizons of anaesthesia during the last 20 years and has led to an increase of basic science articles that are published in the specialised anaesthetic journals or originate in anaesthetic institutions. We searched for and analysed the specific features, such as year of publication, publishing journal, and country of origin, of all such molecular biology articles stored in the MEDLINE database during the period 1986-2002. We identified 1265 original articles that used molecular biology techniques; 223 (18%) of these articles were published in anaesthetic journals and 1042 (82%) articles in 556 other biomedical journals. While in the late 1980s only a few molecular biology articles were published each year by anaesthetic institutions, worldwide this number reached approximately 200 basic science articles by the end of 2002. The USA clearly dominates the field of anaesthesia with respect to molecular biology research with 839 (66%) such articles.

Motivational profiles and their relationships with basic psychological needs, academic performance, study strategies, self-esteem, and vitality in dental students in Chile.

PubMed

Orsini, Cesar A; Binnie, Vivian I; Tricio, Jorge A

2018-01-01

To determine dental students' motivational profiles through a person-centred approach and to analyse the associations with the satisfaction of their basic psychological needs, study strategies, academic performance, self-esteem, and vitality. A total of 924 students from the University of San Sebastian (Chile) participated in this cross-sectional cor¬relational study in spring 2016. Data were collected through 5 self-reported instruments, in addition to students' academic performance. The Cronbach alpha, descriptive statistics, and correla¬tion scores were computed. A k-means cluster analysis with intrinsic and controlled motivation was conducted to identify different mo-tivational profiles. Subsequently, multivariate analysis of covariance controlling for the effects of gender and year of study was carried out to assess differences among the retained motivational profiles and learning variables. All instruments showed acceptable Cronbach alpha scores. A 4-cluster solution was retained for the motivational profile over a 3- or 5-cluster solution. Students' motiva-tional profiles were characterized by different degrees of intrinsic and controlled motivation. The high intrinsic motivation groups showed higher perceptions of their basic psychological, a greater propensity for a deep rather than surface study strategy, better academic performance, and higher scores for self-esteem and vitality than the low intrinsic motivation groups, regardless of the degree of controlled motivation. Students with a high intrinsic motivation profile, regardless of their controlled motivation scores, reported better learning characteristics. Therefore, special attention should be paid to students' motivational profiles, as the quality of motivation might serve as a basis for interventions to support their academic success and well-being.

Introduction to molecular topology: basic concepts and application to drug design.

PubMed

Gálvez, Jorge; Gálvez-Llompart, María; García-Domenech, Ramón

2012-09-01

In this review it is dealt the use of molecular topology (MT) in the selection and design of new drugs. After an introduction of the actual methods used for drug design, the basic concepts of MT are defined, including examples of calculation of topological indices, which are numerical descriptors of molecular structures. The goal is making this calculation familiar to the potential students and allowing a straightforward comprehension of the topic. Finally, the achievements obtained in this field are detailed, so that the reader can figure out the great interest of this approach.

Vascular tissue engineering: towards the next generation vascular grafts.

PubMed

Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

2011-04-30

The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. Published by Elsevier B.V.

MOLEonline 2.0: interactive web-based analysis of biomacromolecular channels.

PubMed

Berka, Karel; Hanák, Ondrej; Sehnal, David; Banás, Pavel; Navrátilová, Veronika; Jaiswal, Deepti; Ionescu, Crina-Maria; Svobodová Vareková, Radka; Koca, Jaroslav; Otyepka, Michal

2012-07-01

Biomolecular channels play important roles in many biological systems, e.g. enzymes, ribosomes and ion channels. This article introduces a web-based interactive MOLEonline 2.0 application for the analysis of access/egress paths to interior molecular voids. MOLEonline 2.0 enables platform-independent, easy-to-use and interactive analyses of (bio)macromolecular channels, tunnels and pores. Results are presented in a clear manner, making their interpretation easy. For each channel, MOLEonline displays a 3D graphical representation of the channel, its profile accompanied by a list of lining residues and also its basic physicochemical properties. The users can tune advanced parameters when performing a channel search to direct the search according to their needs. The MOLEonline 2.0 application is freely available via the Internet at http://ncbr.muni.cz/mole or http://mole.upol.cz.

Ohio Workplace Education Resource Guide.

ERIC Educational Resources Information Center

Northwest ABLE Resource Center, Toledo, OH.

This manual is designed for adult basic education programs to use as a resource for workplace education (WE). It begins with a section of introductory materials, including a WE definition, scope of work, and survey results. The next section contains a program profile; director/coordinator profile; instructor profiles; Ohio ABLE workplace site…

Profile of Specialist Teachers in Elementary Schools: Fine Arts.

ERIC Educational Resources Information Center

Bachelor, Barry G.

The characteristics of elementary teachers of music, art, and drama in 14 southern California counties are profiled. The source data for the profile were the Professional Assignment Information Forms of the California Basic Educational Data System, completed annually by every certificated employee in California's public schools. The…

Asian Pacific Americans in Cambridge. Community Profiles in Massachusetts.

ERIC Educational Resources Information Center

Massachusetts Univ., Boston. Inst. for Asian American Studies.

The Community Profiles Project uses data from the 1990 U.S. Census to describe some of the population characteristics of Asian Pacific Americans in selected Massachusetts cities and towns. The profiles include basic statistics relating to income, employment, education, and housing. This information can assist policy makers and practitioners in…

Mission Assurance Analysis of Theater Ballistic Missile Defense Systems

DTIC Science & Technology

2011-09-01

7  Figure 2. MOSAIC Management Paradigm ( Alberts et. al., 2008) .................................. 14  Figure 3. Basic...Success Profiles ( Alberts , et. al., 2008) ................................................... 16  Figure 4. Success Profile with Uncertainty Range... Alberts , et. al., 2008) ....................... 16  Figure 5. Success Profile with Event Sensitivity ( Alberts , et. al., 2008) .......................... 17

Molecular profiling and commercial predication assays in ovarian cancer: still not ready for prime time?

PubMed

Kohn, Elise C

2014-01-01

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach-rather than undergoing rigorous scientific examination-is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

Exhaled molecular profiles in the assessment of cystic fibrosis and primary ciliary dyskinesia.

PubMed

Paff, T; van der Schee, M P; Daniels, J M A; Pals, G; Postmus, P E; Sterk, P J; Haarman, E G

2013-09-01

Early diagnosis and monitoring of disease activity are essential in cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). We aimed to establish exhaled molecular profiles as the first step in assessing the potential of breath analysis. Exhaled breath was analyzed by electronic nose in 25 children with CF, 25 with PCD and 23 controls. Principle component reduction and canonical discriminant analysis were used to construct internally cross-validated ROC curves. CF and PCD patients had significantly different breath profiles when compared to healthy controls (CF: sensitivity 84%, specificity 65%; PCD: sensitivity 88%, specificity 52%) and from each other (sensitivity 84%, specificity 60%). Patients with and without exacerbations had significantly different breath profiles (CF: sensitivity 89%, specificity 56%; PCD: sensitivity 100%, specificity 90%). Exhaled molecular profiles significantly differ between patients with CF, PCD and controls. The eNose may have potential in disease monitoring based on the influence of exacerbations on the VOC-profile. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Quantum Dot Platform for Single-Cell Molecular Profiling

NASA Astrophysics Data System (ADS)

Zrazhevskiy, Pavel S.

In-depth understanding of the nature of cell physiology and ability to diagnose and control the progression of pathological processes heavily rely on untangling the complexity of intracellular molecular mechanisms and pathways. Therefore, comprehensive molecular profiling of individual cells within the context of their natural tissue or cell culture microenvironment is essential. In principle, this goal can be achieved by tagging each molecular target with a unique reporter probe and detecting its localization with high sensitivity at sub-cellular resolution, primarily via microscopy-based imaging. Yet, neither widely used conventional methods nor more advanced nanoparticle-based techniques have been able to address this task up to date. High multiplexing potential of fluorescent probes is heavily restrained by the inability to uniquely match probes with corresponding molecular targets. This issue is especially relevant for quantum dot probes---while simultaneous spectral imaging of up to 10 different probes is possible, only few can be used concurrently for staining with existing methods. To fully utilize multiplexing potential of quantum dots, it is necessary to design a new staining platform featuring unique assignment of each target to a corresponding quantum dot probe. This dissertation presents two complementary versatile approaches towards achieving comprehensive single-cell molecular profiling and describes engineering of quantum dot probes specifically tailored for each staining method. Analysis of expanded molecular profiles is achieved through augmenting parallel multiplexing capacity with performing several staining cycles on the same specimen in sequential manner. In contrast to other methods utilizing quantum dots or other nanoparticles, which often involve sophisticated probe synthesis, the platform technology presented here takes advantage of simple covalent bioconjugation and non-covalent self-assembly mechanisms for straightforward probe preparation and specimen labeling, requiring no advanced technical skills and being directly applicable for a wide range of molecular profiling studies. Utilization of quantum dot platform for single-cell molecular profiling promises to greatly benefit both biomedical research and clinical diagnostics by providing a tool for addressing phenotypic heterogeneity within large cell populations, opening access to studying low-abundance events often masked or completely erased by batch processing, and elucidating biomarker signatures of diseases critical for accurate diagnostics and targeted therapy.

Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.

PubMed

Köbel, Martin; Meng, Bo; Hoang, Lien N; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C Blake; Lee, Cheng-Han

2016-02-01

Mixed endometrial carcinoma refers to a tumor that comprises 2 or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas-11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade ECs (CCC/EC), and 2 mixed CCC and SCs (CCC/SC), using targeted next-generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC, and 1 SC/CCC) showed an SC molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch-repair protein deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and 1 EC/CCC case showed both shared and unique molecular features in the 2 histotype components, suggesting early molecular divergence from a common clonal origin. In 2 cases, there were no shared molecular features, and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphologic mimicry, whereby tumors with serous-type molecular profile show morphologic features of EC or CCC, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors).

Molecular analysis of mixed endometrial carcinomas shows clonality in most cases

PubMed Central

Hoang, Lien N.; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C. Blake; Lee, Cheng-Han

2016-01-01

Mixed endometrial carcinoma refers to a tumor that is comprised of two or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas - 11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade endometrioid carcinomas (CCC/EC), and 2 mixed clear cell and serous carcinoma (CCC/SC), using targeted next generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC and 1 SC/CCC) showed a serous carcinoma molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch repair protein (MMR) deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and one EC/CCC case showed both shared and unique molecular features in the two histotype components, suggesting early molecular divergence from a common clonal origin. In two cases, there were no shared molecular features and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphological mimicry, whereby tumors with serous-type molecular profile show morphological features of endometrioid or clear cell carcinoma, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors). PMID:26492180

Profiles of Learning. The Basic Skills Testing Program in New South Wales: 1989.

ERIC Educational Resources Information Center

Masters, Geofferey; And Others

This publication on the New South Wales' Basic Skills Testing Program (BSTP) describes the development of the program's tests, the analysis of students' results, and the communication of results to parents, teachers, and schools. In BSTP tests, basic skills are defined not as low-level, rudimentary survival skills, but as major areas of learning…

Interaction of a sodium ion with the water liquid-vapor interface

NASA Technical Reports Server (NTRS)

Wilson, M. A.; Pohorille, A.; Pratt, L. R.; MacElroy, R. D. (Principal Investigator)

1989-01-01

Molecular dynamics results are presented for the density profile of a sodium ion near the water liquid-vapor interface at 320 K. These results are compared with the predictions of a simple dielectric model for the interaction of a monovalent ion with this interface. The interfacial region described by the model profile is too narrow and the profile decreases too abruptly near the solution interface. Thus, the simple model does not provide a satisfactory description of the molecular dynamics results for ion positions within two molecular diameters from the solution interface where appreciable ion concentrations are observed. These results suggest that surfaces associated with dielectric models of ionic processes at aqueous solution interfaces should be located at least two molecular diameters inside the liquid phase. A free energy expense of about 2 kcal/mol is required to move the ion within two molecular layers of the free water liquid-vapor interface.

Generalized Models for Rock Joint Surface Shapes

PubMed Central

Du, Shigui; Hu, Yunjin; Hu, Xiaofei

2014-01-01

Generalized models of joint surface shapes are the foundation for mechanism studies on the mechanical effects of rock joint surface shapes. Based on extensive field investigations of rock joint surface shapes, generalized models for three level shapes named macroscopic outline, surface undulating shape, and microcosmic roughness were established through statistical analyses of 20,078 rock joint surface profiles. The relative amplitude of profile curves was used as a borderline for the division of different level shapes. The study results show that the macroscopic outline has three basic features such as planar, arc-shaped, and stepped; the surface undulating shape has three basic features such as planar, undulating, and stepped; and the microcosmic roughness has two basic features such as smooth and rough. PMID:25152901

78 FR 32260 - Center For Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... 20892, (301) 435-4445, [email protected] . Name of Committee: Oncology 1-Basic Translational... . Name of Committee: Oncology 1-Basic Translational Integrated Review Group Molecular Oncogenesis Study...

Basic Energy Science | NREL

Science.gov Websites

scientific understanding-of molecular, nanoscale, semiconductor, and biological materials, systems, and molecular, nanoscale, and semiconductor systems to capture, control, and convert solar radiation with high

Solvent Chemistry in the Electronic Cigarette Reaction Vessel

NASA Astrophysics Data System (ADS)

Jensen, R. Paul; Strongin, Robert M.; Peyton, David H.

2017-02-01

Knowledge of the mechanism of formation, levels and toxicological profiles of the chemical products in the aerosols (i.e., vapor plus particulate phases) of e-cigarettes is needed in order to better inform basic research as well as the general public, regulators, and industry. To date, studies of e-cigarette emissions have mainly focused on chromatographic techniques for quantifying and comparing the levels of selected e-cigarette aerosol components to those found in traditional cigarettes. E-cigarettes heat and aerosolize the solvents propylene glycol (PG) and glycerol (GLY), thereby affording unique product profiles as compared to traditional cigarettes. The chemical literature strongly suggests that there should be more compounds produced by PG and GLY than have been reported in e-cigarette aerosols to date. Herein we report an extensive investigation of the products derived from vaporizing PG and GLY under mild, single puff conditions. This has led to the discovery of several new compounds produced under vaping conditions. Prior reports on e-cigarette toxin production have emphasized temperature as the primary variable in solvent degradation. In the current study, the molecular pathways leading to enhanced PG/GLY reactivity are described, along with the most impactful chemical conditions promoting byproduct production.

Monte Carlo simulation of electrothermal atomization on a desktop personal computer

NASA Astrophysics Data System (ADS)

Histen, Timothy E.; Güell, Oscar A.; Chavez, Iris A.; Holcombea, James A.

1996-07-01

Monte Carlo simulations have been applied to electrothermal atomization (ETA) using a tubular atomizer (e.g. graphite furnace) because of the complexity in the geometry, heating, molecular interactions, etc. The intense computational time needed to accurately model ETA often limited its effective implementation to the use of supercomputers. However, with the advent of more powerful desktop processors, this is no longer the case. A C-based program has been developed and can be used under Windows TM or DOS. With this program, basic parameters such as furnace dimensions, sample placement, furnace heating and kinetic parameters such as activation energies for desorption and adsorption can be varied to show the absorbance profile dependence on these parameters. Even data such as time-dependent spatial distribution of analyte inside the furnace can be collected. The DOS version also permits input of external temperaturetime data to permit comparison of simulated profiles with experimentally obtained absorbance data. The run-time versions are provided along with the source code. This article is an electronic publication in Spectrochimica Acta Electronica (SAE), the electronic section of Spectrochimica Acta Part B (SAB). The hardcopy text is accompanied by a diskette with a program (PC format), data files and text files.

Relationship of carbohydrates and lignin molecular structure spectral profiles to nutrient profile in newly developed oats cultivars and barley grain

NASA Astrophysics Data System (ADS)

Prates, Luciana Louzada; Refat, Basim; Lei, Yaogeng; Louzada-Prates, Mariana; Yu, Peiqiang

2018-01-01

The objectives of this study were to quantify the chemical profile and the magnitude of differences in the oat and barley grain varieties developed by Crop Development Centre (CDC) in terms of Cornell Net Carbohydrate Protein System (CNCPS) carbohydrate sub-fractions: CA4 (sugars), CB1 (starch), CB2 (soluble fibre), CB3 (available neutral detergent fibre - NDF), and CC (unavailable carbohydrate); to estimate the energy values; to detect the lignin and carbohydrate (CHO) molecular structure profiles in CDC Nasser and CDC Seabiscuit oat and CDC Meredith barley grains by using Fourier transform infrared attenuated total reflectance (FTIR-ATR); to develop a model to predict nutrient supply based on CHO molecular profile. Results showed that NDF, ADF and CHO were greater (P < 0.05) in oat than in barley. The starch content was greater (P < 0.05) in barley than in oat. The CDC Meredith showed greater total rumen degradable carbohydrate (RDC), intestinal digestible fraction carbohydrate (FC) and lower total rumen undegradable carbohydrate (RUC). However, the estimated milk production did not differ for CDC Nasser oat and CDC Meredith barley. Lignin peak area and peak height did not differ (P > 0.05) for oat and barley grains as well as non-structural CHO. However, cellulosic compounds peak area and height were greater (P < 0.05) in oat than barley grains. Multiple regressions were determined to predict nutrient supply by using lignin and CHO molecular profiles. It was concluded that although there were some differences between oat and barley grains, CDC Nasser and CDC Meredith presented similarities related to chemical and molecular profiles, indicating that CDC Meredith barley could be replaced for CDC Nasser as ruminant feed. The FTIR was able to identify functional groups related to CHO molecular spectral in oat and barley grains and FTIR-ATR results could be used to predict nutrient supply in ruminant livestock systems.

Molecular Profiling of Liquid Biopsy Samples for Precision Medicine.

PubMed

Campos, Camila D M; Jackson, Joshua M; Witek, Małgorzata A; Soper, Steven A

In the context of oncology, liquid biopsies consist of harvesting cancer biomarkers, such as circulating tumor cells, tumor-derived cell-free DNA, and extracellular vesicles, from bodily fluids. These biomarkers provide a source of clinically actionable molecular information that can enable precision medicine. Herein, we review technologies for the molecular profiling of liquid biopsy markers with special emphasis on the analysis of low abundant markers from mixed populations.

Impact of Physical Activity on Obesity and Lipid Profile of Adults with Intellectual Disability

ERIC Educational Resources Information Center

Gawlik, Krystyna; Zwierzchowska, Anna; Celebanska, Diana

2018-01-01

Introduction: This study assessed overweight, obesity and lipid profiles in adults with intellectual disability and compared these metrics with their physical activity. Materials and Method: Basic somatic parameters, lipid profile and weekly physical activity were examined in 27 adults with moderate intellectual disability. Chi-square independence…

Hegemonic structure of basic, clinical and patented knowledge on Ebola research: a US army reductionist initiative.

PubMed

Fajardo-Ortiz, David; Ortega-Sánchez-de-Tagle, José; Castaño, Victor M

2015-04-19

Ebola hemorrhagic fever (Ebola) is still a highly lethal infectious disease long affecting mainly neglected populations in sub-Saharan Africa. Moreover, this disease is now considered a potential worldwide threat. In this paper, we present an approach to understand how the basic, clinical and patent knowledge on Ebola is organized and intercommunicated and what leading factor could be shaping the evolution of the knowledge translation process for this disease. A combination of citation network analysis; analysis of Medical heading Subject (MeSH) and Gene Ontology (GO) terms, and quantitative content analysis for patents and scientific literature, aimed to map the organization of Ebola research was carried out. We found six putative research fronts (i.e. clusters of high interconnected papers). Three research fronts are basic research on Ebola virus structural proteins: glycoprotein, VP40 and VP35, respectively. There is a fourth research front of basic research papers on pathogenesis, which is the organizing hub of Ebola research. A fifth research front is pre-clinical research focused on vaccines and glycoproteins. Finally, a clinical-epidemiology research front related to the disease outbreaks was identified. The network structure of patent families shows that the dominant design is the use of Ebola virus proteins as targets of vaccines and other immunological treatments. Therefore, patents network organization resembles the organization of the scientific literature. Specifically, the knowledge on Ebola would flow from higher (clinical-epidemiology) to intermediated (cellular-tissular pathogenesis) to lower (molecular interactions) levels of organization. Our results suggest a strong reductionist approach for Ebola research probably influenced by the lethality of the disease. On the other hand, the ownership profile of the patent families network and the main researches relationship with the United State Army suggest a strong involvement of this military institution in Ebola research.

Non-linear optical techniques and optical properties of condensed molecular systems

NASA Astrophysics Data System (ADS)

Citroni, Margherita

2013-06-01

Structure, dynamics, and optical properties of molecular systems can be largely modified by the applied pressure, with remarkable consequences on their chemical stability. Several examples of selective reactions yielding technologically attractive products can be cited, which are particularly efficient when photochemical effects are exploited in conjunction with the structural conditions attained at high density. Non-linear optical techniques are a basic tool to unveil key aspects of the chemical reactivity and dynamic properties of molecules. Their application to high-pressure samples is experimentally challenging, mainly because of the small sample dimensions and of the non-linear effects generated in the anvil materials. In this talk I will present results on the electronic spectra of several aromatic crystals obtained through two-photon induced fluorescence and two-photon excitation profiles measured as a function of pressure (typically up to about 25 GPa), and discuss the relationship between the pressure-induced modifications of the electronic structure and the chemical reactivity at high pressure. I will also present the first successful pump-probe infrared measurement performed as a function of pressure on a condensed molecular system. The system under examination is liquid water, in a sapphire anvil cell, up to 1 GPa along isotherms at 298 and 363 K. These measurements give a new enlightening insight into the dynamical properties of low- and high-density water allowing a definition of the two structures.

Field-Theoretic Simulations

NASA Astrophysics Data System (ADS)

Ganesan, Venkat; Fredrickson, Glenn H.

The science and engineering of materials is entering a new era of so-called "designer materials", wherein, based upon the properties required for a particular application, a material is designed by exploiting the self-assembly of appropriately chosen molecular constituents [1]. The desirable and marketable properties of such materials, which include plastic alloys, block and graft copolymers, and polyelectrolyte solutions, complexes, and gels, depend critically on the ability to control and manipulate morphology by adjusting a combination of molecular and macroscopic variables. For example, styrenebutadiene block copolymers can be devised that serve either as rigid, tough, transparent thermoplastics or as soft, flexible, thermoplastic elastomers, by appropriate control of copolymer architecture and styrene/butadiene ratio. In this case, the property profiles are intimately connected to the extent and type of nanoscale self-assembly that is established within the material. One of the main challenges confronting the successful design of nano-structured polymers is the development of a basic understanding of the relationship between the molecular details of the polymer formulation and the morphology that is achieved. Unfortunately, such relationships are still mainly determined by trial and error experimentation. A purely experimental-based program in pursuit of this objective proves cumbersome — primarily, due to the broad parameter space accessible at the time of synthesis and formulation. Consequently, there is a significant motivation for the development of computational tools that can enable a rational exploration of the parameter space.

Profile of Knowledge Management, Basic Sanitation and Attitudes towards Clean and Health Community in Kupang City

ERIC Educational Resources Information Center

Nikmah; Ardi, Muhammad; Yahya, Mohamad; Upa, Muhamad D. Pua; Dirawan, Gufran Darma

2017-01-01

The objective of research is to describe the knowledge and attitude of basic sanitation management community in Kupang City. This type of research is a survey research using quantitative approach. Data were collected by using the instrument in the form of test knowledge of basic sanitation management and attitude questionnaire. The data was then…

NEW MOLECULAR MEDICINE-BASED SCAR MANAGEMENT STRATEGIES

PubMed Central

Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G

2014-01-01

Keloids and hypertrophic scars are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research has contributed to unravel new bench-to-bedside scar therapies, and to dissect the complex signaling pathways involved. Peptides such as transforming growth factor beta (TGF-β) superfamily, with SMADs, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-β4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scars. The aim of this review is to describe the basic complexity of these new molecular scar management strategies, and point out new fibrosis research lines. PMID:24438742

Bio-functions and molecular carbohydrate structure association study in forage with different source origins revealed using non-destructive vibrational molecular spectroscopy techniques

NASA Astrophysics Data System (ADS)

Ji, Cuiying; Zhang, Xuewei; Yan, Xiaogang; Mostafizar Rahman, M.; Prates, Luciana L.; Yu, Peiqiang

2017-08-01

The objectives of this study were to: 1) investigate forage carbohydrate molecular structure profiles; 2) bio-functions in terms of CHO rumen degradation characteristics and hourly effective degradation ratio of N to OM (HEDN/OM), and 3) quantify interactive association between molecular structures, bio-functions and nutrient availability. The vibrational molecular spectroscopy was applied to investigate the structure feature on a molecular basis. Two sourced-origin alfalfa forages were used as modeled forages. The results showed that the carbohydrate molecular structure profiles were highly linked to the bio-functions in terms of rumen degradation characteristics and hourly effective degradation ratio. The molecular spectroscopic technique can be used to detect forage carbohydrate structure features on a molecular basis and can be used to study interactive association between forage molecular structure and bio-functions.

Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans.

PubMed

Carter, Philip; Alifrangis, Costi; Cereser, Biancastella; Chandrasinghe, Pramodh; Del Bel Belluz, Lisa; Moderau, Nina; Poyia, Fotini; Schwartzberg, Lee S; Tabassum, Neha; Wen, Jinrui; Krell, Jonathan; Stebbing, Justin

2018-04-03

We used data obtained by Caris Life Sciences, to evaluate the benefits of tailoring treatments for a breast carcinoma cohort by using tumor molecular profiles to inform decisions. Data for 92 breast cancer patients from the commercial Caris Molecular Intelligence database was retrospectively divided into two groups, so that the first always followed treatment recommendations, whereas in the second group all patients received at least one drug after profiling that was predicted to lack benefit. The biomarker and drug associations were based on tests including fluorescent in situ hybridization and DNA sequencing, although immunohistochemistry was the main test used. Patients whose drugs matched those recommended according to their tumor profile had an average overall survival of 667 days, compared to 510 days for patients that did not (P=0.0316). In the matched treatment group, 26% of patients were deceased by the last time of monitoring, whereas this was 41% in the unmatched group (P=0.1257). We therefore confirm the ability of tumor molecular profiling to improve survival of breast cancer patients. Immunohistochemistry biomarkers for the androgen, estrogen and progesterone receptors were found to be prognostic for survival.

Strong-field Photoionization of Sputtered Neutral Molecules for Molecular Depth Profiling

PubMed Central

Willingham, D; Brenes, D. A.; Wucher, A

2009-01-01

Molecular depth profiles of an organic thin film of guanine vapor deposited onto a Ag substrate are obtained using a 40 keV C60 cluster ion beam in conjunction with time-of-flight secondary ion mass spectrometric (ToF-SIMS) detection. Strong-field, femtosecond photoionization of intact guanine molecules is used to probe the neutral component of the profile for direct comparison with the secondary ion component. The ability to simultaneously acquire secondary ions and photoionized neutral molecules reveals new fundamental information about the factors that influence the properties of the depth profile. Results show that there is an increased ionization probability for protonated molecular ions within the first 10 nm due to the generation of free protons within the sample. Moreover, there is a 50% increase in fragment ion signal relative to steady state values 25 nm before reaching the guanine/Ag interface as a result of interfacial chemical damage accumulation. An altered layer thickness of 20 nm is observed as a consequence of ion beam induced chemical mixing. In general, we show that the neutral component of a molecular depth profile using the strong-field photoionization technique can be used to elucidate the effects of variations in ionization probability on the yield of molecular ions as well as to aid in obtaining accurate information about depth dependent chemical composition that cannot be extracted from TOF-SIMS data alone. PMID:20495665

Motor potential profile and a robust method for extracting it from time series of motor positions.

PubMed

Wang, Hongyun

2006-10-21

Molecular motors are small, and, as a result, motor operation is dominated by high-viscous friction and large thermal fluctuations from the surrounding fluid environment. The small size has hindered, in many ways, the studies of physical mechanisms of molecular motors. For a macroscopic motor, it is possible to observe/record experimentally the internal operation details of the motor. This is not yet possible for molecular motors. The chemical reaction in a molecular motor has many occupancy states, each having a different effect on the motor motion. The overall effect of the chemical reaction on the motor motion can be characterized by the motor potential profile. The potential profile reveals how the motor force changes with position in a motor step, which may lead to insights into how the chemical reaction is coupled to force generation. In this article, we propose a mathematical formulation and a robust method for constructing motor potential profiles from time series of motor positions measured in single molecule experiments. Numerical examples based on simulated data are shown to demonstrate the method. Interestingly, it is the small size of molecular motors (negligible inertia) that makes it possible to recover the potential profile from time series of motor positions. For a macroscopic motor, the variation of driving force within a cycle is smoothed out by the large inertia.

LiGRO: a graphical user interface for protein-ligand molecular dynamics.

PubMed

Kagami, Luciano Porto; das Neves, Gustavo Machado; da Silva, Alan Wilter Sousa; Caceres, Rafael Andrade; Kawano, Daniel Fábio; Eifler-Lima, Vera Lucia

2017-10-04

To speed up the drug-discovery process, molecular dynamics (MD) calculations performed in GROMACS can be coupled to docking simulations for the post-screening analyses of large compound libraries. This requires generating the topology of the ligands in different software, some basic knowledge of Linux command lines, and a certain familiarity in handling the output files. LiGRO-the python-based graphical interface introduced here-was designed to overcome these protein-ligand parameterization challenges by allowing the graphical (non command line-based) control of GROMACS (MD and analysis), ACPYPE (ligand topology builder) and PLIP (protein-binder interactions monitor)-programs that can be used together to fully perform and analyze the outputs of complex MD simulations (including energy minimization and NVT/NPT equilibration). By allowing the calculation of linear interaction energies in a simple and quick fashion, LiGRO can be used in the drug-discovery pipeline to select compounds with a better protein-binding interaction profile. The design of LiGRO allows researchers to freely download and modify the software, with the source code being available under the terms of a GPLv3 license from http://www.ufrgs.br/lasomfarmacia/ligro/ .

Understanding nanofluid stability through molecular simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dang, Liem X.; Annapureddy, Harsha V.; Sun, Xiuquan

We performed molecular dynamics simulations to study solvation of a nanoparticle and nanoparticle-nanoparticle interactions in an n-hexane solution. Structural signatures are barely observed between the nanoparticle and n-hexane molecules because of weak binding and steric effects. The dynamic properties of the n-hexane molecule, on the other hand, are significantly influenced by the solvated nanoparticle. The diffusion of n-hexane molecules inside the nanoparticle is significantly decreased mainly because of the loss of dimensions of translation. Because one translational degree of freedom is lost by colliding with the wall of nanoparticle, the n-hexane molecules outside the nanoparticle diffuse 30% slower than themore » molecules in pure solution. The computed free energy profiles illustrate that the arrangement of the nanoparticles in bulk n-hexane solution are dependent on the orientation and functional group. We found that the n-hexane solvent exerts some effects on the interactions between the solvated nanoparticles. This work was supported by the US Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences and by the Office of Energy Efficiency and Renewable Energy, Geothermal Technologies Program. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle.« less

Electrospray Ionization Efficiency Is Dependent on Different Molecular Descriptors with Respect to Solvent pH and Instrumental Configuration

PubMed Central

Kiontke, Andreas; Oliveira-Birkmeier, Ariana; Opitz, Andreas

2016-01-01

Over the past decades, electrospray ionization for mass spectrometry (ESI-MS) has become one of the most commonly employed techniques in analytical chemistry, mainly due to its broad applicability to polar and semipolar compounds and the superior selectivity which is achieved in combination with high resolution separation techniques. However, responsiveness of an analytical method also determines its suitability for the quantitation of chemical compounds; and in electrospray ionization for mass spectrometry, it can vary significantly among different analytes with identical solution concentrations. Therefore, we investigated the ESI-response behavior of 56 nitrogen-containing compounds including aromatic amines and pyridines, two compound classes of high importance to both, synthetic organic chemistry as well as to pharmaceutical sciences. These compounds are increasingly analyzed employing ESI mass spectrometry detection due to their polar, basic character. Signal intensities of the peaks from the protonated molecular ion (MH+) were acquired under different conditions and related to compound properties such as basicity, polarity, volatility and molecular size exploring their quantitative impact on ionization efficiency. As a result, we found that though solution basicity of a compound is the main factor initially determining the ESI response of the protonated molecular ion, other factors such as polarity and vaporability become more important under acidic solvent conditions and may nearly outweigh the importance of basicity under these conditions. Moreover, we show that different molecular descriptors may become important when using different types of instruments for such investigations, a fact not detailed so far in the available literature. PMID:27907110

Genomic Signal Processing: Predicting Basic Molecular Biological Principles

NASA Astrophysics Data System (ADS)

Alter, Orly

2005-03-01

Advances in high-throughput technologies enable acquisition of different types of molecular biological data, monitoring the flow of biological information as DNA is transcribed to RNA, and RNA is translated to proteins, on a genomic scale. Future discovery in biology and medicine will come from the mathematical modeling of these data, which hold the key to fundamental understanding of life on the molecular level, as well as answers to questions regarding diagnosis, treatment and drug development. Recently we described data-driven models for genome-scale molecular biological data, which use singular value decomposition (SVD) and the comparative generalized SVD (GSVD). Now we describe an integrative data-driven model, which uses pseudoinverse projection (1). We also demonstrate the predictive power of these matrix algebra models (2). The integrative pseudoinverse projection model formulates any number of genome-scale molecular biological data sets in terms of one chosen set of data samples, or of profiles extracted mathematically from data samples, designated the ``basis'' set. The mathematical variables of this integrative model, the pseudoinverse correlation patterns that are uncovered in the data, represent independent processes and corresponding cellular states (such as observed genome-wide effects of known regulators or transcription factors, the biological components of the cellular machinery that generate the genomic signals, and measured samples in which these regulators or transcription factors are over- or underactive). Reconstruction of the data in the basis simulates experimental observation of only the cellular states manifest in the data that correspond to those of the basis. Classification of the data samples according to their reconstruction in the basis, rather than their overall measured profiles, maps the cellular states of the data onto those of the basis, and gives a global picture of the correlations and possibly also causal coordination of these two sets of states. Mapping genome-scale protein binding data using pseudoinverse projection onto patterns of RNA expression data that had been extracted by SVD and GSVD, a novel correlation between DNA replication initiation and RNA transcription during the cell cycle in yeast, that might be due to a previously unknown mechanism of regulation, is predicted. (1) Alter & Golub, Proc. Natl. Acad. Sci. USA 101, 16577 (2004). (2) Alter, Golub, Brown & Botstein, Miami Nat. Biotechnol. Winter Symp. 2004 (www.med.miami.edu/mnbws/alter-.pdf)

Determinants of Demand in the Public Dental Emergency Service.

PubMed

Matsumoto, Maria Sa; Gatti, Marcia An; de Conti, Marta Hs; de Ap Simeão, Sandra F; de Oliveira Braga Franzolin, Solange; Marta, Sara N

2017-02-01

Although dental emergencies are primarily aimed at pain relief, in practice, dental emergency services have been overwhelmed by the massive inflow of patients with less complex cases, which could be resolved at basic levels of health care. They frequently become the main gateway to the system. We investigated the determinant factors of demand at the Central Dental Emergency Unit in Bauru, São Paulo, Brazil. The questionnaire was applied to 521 users to evaluate sociodemographic profile; factors that led users to seek the service at the central dental emergency; perception of service offered. About 80.4% of users went directly to the central dental emergency, even before seeking basic health units. The reasons were difficulty to be attended (34.6%) and incompatible time (9.8%). To the perception of the necessity of the service, responses were problem as urgent (78.3%) and pain was the main complaint (69.1%). The profile we found was unmarried (41.5%), male (52.2%), white (62.8%), aged 30 to 59 (52.2%), incomplete basic education (41.6%), family income up to 2 minimum wages (47.4%), and no medical/dental plan (88.9%). It was concluded that the users of central dental emergency come from all sectors of the city, due to difficult access to basic health units; they consider their complaint urgent; and they are satisfied with the service offered. To meet the profile of the user urgency's service so that it is not overloaded with demand that can be fulfilled in basic health units.

GENE EXPRESSION PROFILING OF ACCESSIBLE SURROGATE TISSUES TO MONITOR MOLECULAR CHANGES IN INACCESSIBLE TARGET TISSUES FOLLOWING TOXICANT EXPOSURE

EPA Science Inventory

Gene Expression Profiling Of Accessible Surrogate Tissues To Monitor Molecular Changes In Inaccessible Target Tissues Following Toxicant Exposure
John C. Rockett, Chad R. Blystone, Amber K. Goetz, Rachel N. Murrell, Judith E. Schmid and David J. Dix
Reproductive Toxicology ...

75 FR 25273 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

... Genetics Integrated Review Group, Molecular Genetics C Study Section. Date: June 3-4, 2010. Time: 8 a.m. to... Committee: Oncology 1-Basic Translational Integrated Review Group, Cancer Molecular Pathobiology Study... Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Cellular and...

Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets.

PubMed

Van Laere, Steven J; Ueno, Naoto T; Finetti, Pascal; Vermeulen, Peter; Lucci, Anthony; Robertson, Fredika M; Marsan, Melike; Iwamoto, Takayuki; Krishnamurthy, Savitri; Masuda, Hiroko; van Dam, Peter; Woodward, Wendy A; Viens, Patrice; Cristofanilli, Massimo; Birnbaum, Daniel; Dirix, Luc; Reuben, James M; Bertucci, François

2013-09-01

Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported. Affymetrix profiles (HGU133-series) from 137 patients with IBC and 252 patients with non-IBC (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according to the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway, and transcription factor activation. Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (P<0.001), all of which were identified in IBC with a similar prevalence as in nIBC, except for the luminal A subtype (19% vs. 42%; P<0.001) and the HER2-enriched subtype (22% vs. 9%; P<0.001). Supervised analysis identified and validated an IBC-specific, molecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGF-β signaling in IBC. We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGF-β signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner. ©2013 AACR.

Molecular profiling of intrahepatic cholangiocarcinoma: the search for new therapeutic targets.

PubMed

Oliveira, Douglas V N P; Zhang, Shanshan; Chen, Xin; Calvisi, Diego F; Andersen, Jesper B

2017-04-01

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary tumor of the liver and a highly lethal disease. Therapeutic options for advanced iCCA are limited and ineffective due to the largely incomplete understanding of the molecular pathogenesis of this deadly tumor. Areas covered: The present review article outlines the main studies and resulting discoveries on the molecular profiling of iCCA, with a special emphasis on the different techniques used for this purpose, the diagnostic and prognostic markers identified, as well as the genes and pathways that could be potentially targeted with innovative therapies. Expert commentary: Molecular profiling has led to the identification of distinct iCCA subtypes, characterized by peculiar genetic alterations and transcriptomic features. Targeted therapies against some of the identified genes are ongoing and hold great promise to improve the prognosis of iCCA patients.

Design of fluorinated 5-HT(4)R antagonists: influence of the basicity and lipophilicity toward the 5-HT(4)R binding affinities.

PubMed

Fontenelle, Clement Q; Wang, Zhong; Fossey, Christine; Cailly, Thomas; Linclau, Bruno; Fabis, Frederic

2013-12-01

Analogues of potent 5-HT(4)R antagonists possessing a fluorinated N-alkyl chain have been synthesized in order to investigate the effect of the resulting change in basicity and lipophilicity on the affinity and selectivity profile. We demonstrate that for this series, the affinity is decreased with decreased basicity of the piperidine's nitrogen atom. In contrast, the resulting increase in lipophilicity has minimal impact on binding affinity and selectivity. 3,3,3-Trifluoropropyl and 4,4,4-trifluorobutyl derivatives 6d and 6e have shown to bind to the 5-HT(4)R while maintaining their pharmacological profile and selectivity toward other 5-HT receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Growing Arabidopsis in vitro: cell suspensions, in vitro culture, and regeneration.

PubMed

Barkla, Bronwyn J; Vera-Estrella, Rosario; Pantoja, Omar

2014-01-01

An understanding of basic methods in Arabidopsis tissue culture is beneficial for any laboratory working on this model plant. Tissue culture refers to the aseptic growth of cells, organs, or plants in a controlled environment, in which physical, nutrient, and hormonal conditions can all be easily manipulated and monitored. The methodology facilitates the production of a large number of plants that are genetically identical over a relatively short growth period. Techniques, including callus production, cell suspension cultures, and plant regeneration, are all indispensable tools for the study of cellular biochemical and molecular processes. Plant regeneration is a key technology for successful stable plant transformation, while cell suspension cultures can be exploited for metabolite profiling and mining. In this chapter we report methods for the successful and highly efficient in vitro regeneration of plants and production of stable cell suspension lines from leaf explants of both Arabidopsis thaliana and Arabidopsis halleri.

Emerging therapies in allergic conjunctivitis and dry eye syndrome.

PubMed

Nye, Michael; Rudner, Shara; Bielory, Leonard

2013-08-01

Inflammatory disorders of the anterior surface of the eye consist of a spectrum of disorders that range from ocular allergy, dry eye syndrome (DES), and various infections. They exhibit similar pathological profiles, but have divergent immune mechanisms with some overlap. A number of novel treatments are currently being studied that capitalize on the growing understanding of underlying immunopathophysiology. The goal of this review is to examine the emerging pipeline for noninfectious inflammatory disorders of the anterior surface of the eye - primarily allergic conjunctivitis (AC) and DES - in light of the recent basic science discoveries that have fueled their development. Novel molecules for the treatment of AC and DES from clinicaltrials.gov as well as recently filed patents for new molecular entities were reviewed from PUBMED and OVID. Significant progress toward targeted treatments for AC and DES has become increasingly reliant on understanding the immunomodulatory and inflammatory mechanisms of the conjunctiva.

A practical drug discovery project at the undergraduate level.

PubMed

Fray, M Jonathan; Macdonald, Simon J F; Baldwin, Ian R; Barton, Nick; Brown, Jack; Campbell, Ian B; Churcher, Ian; Coe, Diane M; Cooper, Anthony W J; Craven, Andrew P; Fisher, Gail; Inglis, Graham G A; Kelly, Henry A; Liddle, John; Maxwell, Aoife C; Patel, Vipulkumar K; Swanson, Stephen; Wellaway, Natalie

2013-12-01

In this article, we describe a practical drug discovery project for third-year undergraduates. No previous knowledge of medicinal chemistry is assumed. Initial lecture workshops cover the basic principles; then students, in teams, seek to improve the profile of a weakly potent, insoluble phosphatidylinositide 3-kinase delta (PI3Kδ) inhibitor (1) through compound array design, molecular modelling, screening data analysis and the synthesis of target compounds in the laboratory. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. In total, 48 target compounds were prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and ≥tenfold, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Solubility of Gliclazide and Ion-Molecular Interactions with Aminopropanol in Aqueous Solutions

NASA Astrophysics Data System (ADS)

Hamdan, Imad I.; El-Sabawi, Dina; Abu-Dahab, Rana

2018-01-01

A new salt of gliclazide (GZD) was prepared and was shown to have a significantly higher aqueous solubility at physiological pH together with superior dissolution profiles in comparison to GZD employing an organic amino-alcohol base. Characterization by NMR, IR, DSC, conductometry and HPLC techniques concluded that an ion pair salt is formed between acidic GZD and basic aminopropanol (AMP). In addition to the presence of about 5% tightly bound water, hydrogen bonds appeared to form extensively between GZD, AMP and water molecules. Unlike many of solubility enhancing approaches, the salt did not hamper the permeability of GZD as shown by transport through Caco-2 cells model. In vivo studies on rats confirmed that the blood glucose lowering effect of GZD-AMP was significantly higher and more rapid compared to parent GZD indicating an enhanced overall performance of the prepared salt.

Advances in the molecular genetics of gliomas - implications for classification and therapy.

PubMed

Reifenberger, Guido; Wirsching, Hans-Georg; Knobbe-Thomsen, Christiane B; Weller, Michael

2017-07-01

Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.

Profile design for wings and propellers

NASA Technical Reports Server (NTRS)

Quast, A.; Horstmann, K. H.

1984-01-01

It has now become customary to develop profiles for wings and propellers for a given employment of the aircraft. This is possible because methods and computers are available to study an entire series of variants in comparatively short time. The basic viewpoints for profile design are presented. It is shown that laminarization has its advantages in almost all cases, including the design of a turbine blade and the design of the profile of an airliner. The requirements which profiles have to satisfy are discussed along with the possibilities for increasing lift on profiles.

GSyellow, a Multifaceted Tag for Functional Protein Analysis in Monocot and Dicot Plants.

PubMed

Besbrugge, Nienke; Van Leene, Jelle; Eeckhout, Dominique; Cannoot, Bernard; Kulkarni, Shubhada R; De Winne, Nancy; Persiau, Geert; Van De Slijke, Eveline; Bontinck, Michiel; Aesaert, Stijn; Impens, Francis; Gevaert, Kris; Van Damme, Daniel; Van Lijsebettens, Mieke; Inzé, Dirk; Vandepoele, Klaas; Nelissen, Hilde; De Jaeger, Geert

2018-06-01

The ability to tag proteins has boosted the emergence of generic molecular methods for protein functional analysis. Fluorescent protein tags are used to visualize protein localization, and affinity tags enable the mapping of molecular interactions by, for example, tandem affinity purification or chromatin immunoprecipitation. To apply these widely used molecular techniques on a single transgenic plant line, we developed a multifunctional tandem affinity purification tag, named GS yellow , which combines the streptavidin-binding peptide tag with citrine yellow fluorescent protein. We demonstrated the versatility of the GS yellow tag in the dicot Arabidopsis ( Arabidopsis thaliana ) using a set of benchmark proteins. For proof of concept in monocots, we assessed the localization and dynamic interaction profile of the leaf growth regulator ANGUSTIFOLIA3 (AN3), fused to the GS yellow tag, along the growth zone of the maize ( Zea mays ) leaf. To further explore the function of ZmAN3, we mapped its DNA-binding landscape in the growth zone of the maize leaf through chromatin immunoprecipitation sequencing. Comparison with AN3 target genes mapped in the developing maize tassel or in Arabidopsis cell cultures revealed strong conservation of AN3 target genes between different maize tissues and across monocots and dicots, respectively. In conclusion, the GS yellow tag offers a powerful molecular tool for distinct types of protein functional analyses in dicots and monocots. As this approach involves transforming a single construct, it is likely to accelerate both basic and translational plant research. © 2018 American Society of Plant Biologists. All rights reserved.

Optimal molecular profiling of tissue and tissue components: defining the best processing and microdissection methods for biomedical applications.

PubMed

Bova, G Steven; Eltoum, Isam A; Kiernan, John A; Siegal, Gene P; Frost, Andra R; Best, Carolyn J M; Gillespie, John W; Emmert-Buck, Michael R

2005-01-01

Isolation of well-preserved pure cell populations is a prerequisite for sound studies of the molecular basis of pancreatic malignancy and other biological phenomena. This chapter reviews current methods for obtaining anatomically specific signals from molecules isolated from tissues, a basic requirement for productive linking of phenotype and genotype. The quality of samples isolated from tissue and used for molecular analysis is often glossed-over or omitted from publications, making interpretation and replication of data difficult or impossible. Fortunately, recently developed techniques allow life scientists to better document and control the quality of samples used for a given assay, creating a foundation for improvement in this area. Tissue processing for molecular studies usually involves some or all of the following steps: tissue collection, gross dissection/identification, fixation, processing/embedding, storage/archiving, sectioning, staining, microdissection/annotation, and pure analyte labeling/identification. High-quality tissue microdissection does not necessarily mean high-quality samples to analyze. The quality of biomaterials obtained for analysis is highly dependent on steps upstream and downstream from tissue microdissection. We provide protocols for each of these steps, and encourage you to improve upon these. It is worth the effort of every laboratory to optimize and document its technique at each stage of the process, and we provide a starting point for those willing to spend the time to optimize. In our view, poor documentation of tissue and cell type of origin and the use of nonoptimized protocols is a source of inefficiency in current life science research. Even incremental improvement in this area will increase productivity significantly.

Teaching Molecular Biology with Microcomputers.

ERIC Educational Resources Information Center

Reiss, Rebecca; Jameson, David

1984-01-01

Describes a series of computer programs that use simulation and gaming techniques to present the basic principles of the central dogma of molecular genetics, mutation, and the genetic code. A history of discoveries in molecular biology is presented and the evolution of these computer assisted instructional programs is described. (MBR)

Advanced Mass Spectrometry Technologies for the Study of Microbial Pathogenesis

PubMed Central

Moore, Jessica L.; Caprioli, Richard M.; Skaar, Eric P.

2014-01-01

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been successfully applied to the field of microbial pathogenesis with promising results, principally in diagnostic microbiology to rapidly identify bacteria based on the molecular profiles of small cell populations. Direct profiling of molecules from serum and tissue samples by MALDI MS providesa means to study the pathogen-host interaction and to discover potential markers of infection. Systematic molecular profiling across tissue sections represents a new imaging modality, enabling regiospecific molecular measurements to be made in situ, in both two- and three-dimensional analyses. Herein, we briefly summarize work that employs MALDI MS to study the pathogenesis of microbial infection. PMID:24997399

Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

PubMed

Ceccarelli, Michele; Barthel, Floris P; Malta, Tathiane M; Sabedot, Thais S; Salama, Sofie R; Murray, Bradley A; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyun; Rao, Arjun A; Grifford, Mia; Cherniack, Andrew D; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Tirapelli, Daniela Pretti da Cunha; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C; Yung, W K Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J; Lehman, Norman L; Barnholtz-Sloan, Jill S; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D; Laird, Peter W; Gutmann, David H; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G W

2016-01-28

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Preparation of mixed molecularly imprinted polymer magnetic nanoparticles and its application in separation of Chinese traditional medicine

NASA Astrophysics Data System (ADS)

Xie, Yihui; Ma, Yajuan; Bai, Wenting; Zhu, Xiaofang; Liu, Min; Huang, Liping

2017-08-01

A mixed imprinted polymer which can rapidly adsorb all flavonoids from raspberry extract was prepared and recycled. The hybrid molecular surface imprinted polymers were prepared by using quercetin as the template molecule and Fe3O4 magnetic nanospheres as the carrier. The molecular imprinting polymer was prepared by using the "initial template molecule, molecularly imprinted polymer, mixed template molecule, molecularly imprint ted polymers (MIPS)". The adsorption performance and durability of the hybrid molecularly imprinted polymers were investigated by using the fingerprints of the ethyl acetate fraction of raspberry as an index. The adsorption of flavonoids from raspberry extract, lindenoside, cis-lindenin, quercetin, kaempferol and other flavonoids was completely adsorbed by mixed molecular-imprinted polymer, and the other components were basically adsorbed. When Mix-IMPs were repeatedly used 10 times, the fingerprints showed that the content and content of flavonoids were basically the same. The experimental results show that Mix-IMPs has good adsorption performance, can be recycled and used for rapid enrichment of flavonoids in raspberry.

Serial profiles of electrostatic potential in five New Mexico thunderstorms

NASA Astrophysics Data System (ADS)

Stolzenburg, Maribeth; Marshall, Thomas C.

2008-07-01

Profiles of electric potential (V) integrated from balloon-borne electric field (E) measurements are used to investigate the electrical evolution of thunderstorms over the mountains in central New Mexico. With sequential soundings through multiple storms, the time skew associated with obtaining V from a noninstantaneous sounding is also studied. The data show that a basic V profile, with a maximum above a minimum, forms in the early stage of the storm and is maintained throughout its mature stage. Series of soundings from individual storms show only a gradual evolution in the V profile from the early through the mature stage, as the extrema descend in altitude and become shallower and vertically closer together. More evolution occurs in the late stage, when the shape of the V profile reverses to have a minimum above a maximum. The 17 V(z) profiles from the mature stage of five different storms are also very similar in overall shape, suggesting that the basic shape is not significantly affected by differences in lightning flash rate among these storms. The findings indicate that the potential profile during a typical sounding in the mature stage is relatively stable, and the overall shape of the mature stage V profile does not change markedly on the time scale of a particular balloon sounding (10-30 min) through New Mexico mountain storms. Thus time-skew problems in the V profiles are minor during a storm's mature stage.

One-Step Preservation and Decalcification of Bony Tissue for Molecular Profiling.

PubMed

Mueller, Claudius; Harpole, Michael G; Espina, Virginia

2017-01-01

Bone metastasis from primary cancer sites creates diagnostic and therapeutic challenges. Calcified bone is difficult to biopsy due to tissue hardness and patient discomfort, thus limiting the frequency and availability of bone/bone marrow biopsy material for molecular profiling. In addition, bony tissue must be demineralized (decalcified) prior to histomorphologic analysis. Decalcification processes rely on three main principles: (a) solubility of calcium salts in an acid, such as formic or nitric acid; (b) calcium chelation with ethylenediaminetetraacetic acid (EDTA); or (c) ion-exchange resins in a weak acid. A major roadblock in molecular profiling of bony tissue has been the lack of a suitable demineralization process that preserves histomorphology of calcified and soft tissue elements while also preserving phosphoproteins and nucleic acids. In this chapter, we describe general issues relevant to specimen collection and preservation of osseous tissue for molecular profiling. We provide two protocols: (a) one-step preservation of tissue histomorphology and proteins and posttranslational modifications, with simultaneous decalcification of bony tissue, and (b) ethanol-based tissue processing for TheraLin-fixed bony tissue.

Initiative for Molecular Profiling and Advanced Cancer Therapy and challenges in the implementation of precision medicine.

PubMed

Tsimberidou, Apostolia-Maria

In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center. We demonstrated that in patients referred for Phase I clinical trials, the use of tumor molecular profiling and treatment with matched targeted therapy was associated with encouraging rates of response, progression-free survival and overall survival compared to non-matched therapy. We are currently conducting IMPACT2, a randomized study evaluating molecular profiling and targeted agents in patients with metastatic cancer. Optimization of innovative biomarker-driven clinical trials that include targeted therapy and/or immunotherapeutic approaches for carefully selected patients will accelerate the development of novel drugs and the implementation of precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent Advancement of the Molecular Diagnosis in Pediatric Brain Tumor.

PubMed

Bae, Jeong-Mo; Won, Jae-Kyung; Park, Sung-Hye

2018-05-01

Recent discoveries of brain tumor-related genes and fast advances in genomic testing technologies have led to the era of molecular diagnosis of brain tumor. Molecular profiling of brain tumor became the significant step in the diagnosis, the prediction of prognosis and the treatment of brain tumor. Because traditional molecular testing methods have limitations in time and cost for multiple gene tests, next-generation sequencing technologies are rapidly introduced into clinical practice. Targeted sequencing panels using these technologies have been developed for brain tumors. In this article, focused on pediatric brain tumor, key discoveries of brain tumor-related genes are reviewed and cancer panels used in the molecular profiling of brain tumor are discussed.

Recent Advancement of the Molecular Diagnosis in Pediatric Brain Tumor

PubMed Central

Bae, Jeong-Mo; Won, Jae-Kyung; Park, Sung-Hye

2018-01-01

Recent discoveries of brain tumor-related genes and fast advances in genomic testing technologies have led to the era of molecular diagnosis of brain tumor. Molecular profiling of brain tumor became the significant step in the diagnosis, the prediction of prognosis and the treatment of brain tumor. Because traditional molecular testing methods have limitations in time and cost for multiple gene tests, next-generation sequencing technologies are rapidly introduced into clinical practice. Targeted sequencing panels using these technologies have been developed for brain tumors. In this article, focused on pediatric brain tumor, key discoveries of brain tumor-related genes are reviewed and cancer panels used in the molecular profiling of brain tumor are discussed. PMID:29742887

Molecular Mechanisms Underlying the Epileptogenesis and Seizure Progression in Tuberous Sclerosis Complex 1 Deficient Mouse Models

DTIC Science & Technology

2016-10-01

growth and metabolism known as mammalian target of rapamycin complex 1 (mTORC1). The pathological hallmark of TSC brains are cortical tubers...molecule players that respond to or do not respond to mTORC1 inhibitors. We will examine the effects of rapamycin on the molecular changes associated...ribosome profiling and conventional ribosome profiling. Ligation-Free Ribosome Profiling in CamK2a-Cre Tsc1fl/fl Mice following Rapamycin Treatment One

A Diagnostic Assessment for Introductory Molecular and Cell Biology

ERIC Educational Resources Information Center

Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

2010-01-01

We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…

Molecular Mechanics: The Method and Its Underlying Philosophy.

ERIC Educational Resources Information Center

Boyd, Donald B.; Lipkowitz, Kenny B.

1982-01-01

Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

Seth M. Noone | NREL

Science.gov Websites

Education M.S., Biomedical Basic Science, Department of Biochemistry and Molecular Genetics, University of Interaction with Histones H3 and H4," Molecular and Cellular Biology (2013) "The Lysine 48 and Cerevisiae," Molecular and Cellular Biology (2007) View all NREL Publications for Seth M. Noone

Lung tumor diagnosis and subtype discovery by gene expression profiling.

PubMed

Wang, Lu-yong; Tu, Zhuowen

2006-01-01

The optimal treatment of patients with complex diseases, such as cancers, depends on the accurate diagnosis by using a combination of clinical and histopathological data. In many scenarios, it becomes tremendously difficult because of the limitations in clinical presentation and histopathology. To accurate diagnose complex diseases, the molecular classification based on gene or protein expression profiles are indispensable for modern medicine. Moreover, many heterogeneous diseases consist of various potential subtypes in molecular basis and differ remarkably in their response to therapies. It is critical to accurate predict subgroup on disease gene expression profiles. More fundamental knowledge of the molecular basis and classification of disease could aid in the prediction of patient outcome, the informed selection of therapies, and identification of novel molecular targets for therapy. In this paper, we propose a new disease diagnostic method, probabilistic boosting tree (PB tree) method, on gene expression profiles of lung tumors. It enables accurate disease classification and subtype discovery in disease. It automatically constructs a tree in which each node combines a number of weak classifiers into a strong classifier. Also, subtype discovery is naturally embedded in the learning process. Our algorithm achieves excellent diagnostic performance, and meanwhile it is capable of detecting the disease subtype based on gene expression profile.

The development and application of a molecular community profiling strategy to identify polymicrobial bacterial DNA in the whole blood of septic patients.

PubMed

Faria, M M P; Conly, J M; Surette, M G

2015-10-16

The application of molecular based diagnostics in sepsis has had limited success to date. Molecular community profiling methods have indicated that polymicrobial infections are more common than suggested by standard clinical culture. A molecular profiling approach was developed to investigate the propensity for polymicrobial infections in patients predicted to have bacterial sepsis. Disruption of blood cells with saponin and hypotonic shock enabled the recovery of microbial cells with no significant changes in microbial growth when compared to CFU/ml values immediately prior to the addition of saponin. DNA extraction included a cell-wall digestion step with both lysozyme and mutanolysin, which increased the recovery of terminal restriction fragments by 2.4 fold from diverse organisms. Efficiencies of recovery and limits of detection using Illumina sequencing of the 16S rRNA V3 region were determined for both viable cells and DNA using mock bacterial communities inoculated into whole blood. Bacteria from pre-defined communities could be recovered following lysis and removal of host cells with >97% recovery of total DNA present. Applying the molecular profiling methodology to three septic patients in the intensive care unit revealed microbial DNA from blood had consistent alignment with cultured organisms from the primary infection site providing evidence for a bloodstream infection in the absence of a clinical lab positive blood culture result in two of the three cases. In addition, the molecular profiling indicated greater diversity was present in the primary infection sample when compared to clinical diagnostic culture. A method for analyzing bacterial DNA from whole blood was developed in order to characterize the bacterial DNA profile of sepsis infections. Preliminary results indicated that sepsis infections were polymicrobial in nature with the bacterial DNA recovered suggesting a more complex etiology when compared to blood culture data.

Computational investigation of the conformational profile of the four stereomers of Ac-L-Pro-c3Phe-NHMe (c3Phe= 2,3-methanophenylalanine).

PubMed

Rodriguez, Alejandro; Canto, Josep; Corcho, Francesc J; Perez, Juan J

2009-01-01

The present report regards a computational study aimed at assessing the conformational profile of the four stereoisomers of the peptide Ace-Pro-c3Phe-NMe, previously reported to exhibit beta-turn structures in dichloromethane with different type I/type II beta-turn profiles. Molecular systems were represented at the molecular mechanics level using the parm96 parameterization of the AMBER force field. Calculations were carried out in dichloromethane using an implicit solvent approach. Characterization of the conformational features of the peptide analogs was carried out using simulated annealing (SA), molecular dynamics (MD) and replica exchange molecular dynamics (REMD). Present results show that MD calculations do not provide a reasonable sampling after 300 ns. In contrast, both SA and REMD provide similar results and agree well with experimental observations. Copyright 2009 Wiley Periodicals, Inc.

Molecular classification and molecular forecasting of breast cancer: ready for clinical application?

PubMed

Brenton, James D; Carey, Lisa A; Ahmed, Ahmed Ashour; Caldas, Carlos

2005-10-10

Profiling breast cancer with expression arrays has become common, and it has been suggested that the results from early studies will lead to understanding of the molecular differences between clinical cases and allow individualization of care. We critically review two main applications of expression profiling; studies unraveling novel breast cancer classifications and those that aim to identify novel markers for prediction of clinical outcome. Breast cancer may now be subclassified into luminal, basal, and HER2 subtypes with distinct differences in prognosis and response to therapy. However, profiling studies to identify predictive markers have suffered from methodologic problems that prevent general application of their results. Future work will need to reanalyze existing microarray data sets to identify more representative sets of candidate genes for use as prognostic signatures and will need to take into account the new knowledge of molecular subtypes of breast cancer when assessing predictive effects.

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

PubMed Central

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

2009-01-01

Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

PubMed

Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Küppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

2014-04-01

Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

Country Education Profiles: Algeria.

ERIC Educational Resources Information Center

International Bureau of Education, Geneva (Switzerland).

One of a series of profiles prepared by the Cooperative Educational Abstracting Service, this brief outline provides basic background information on educational principles, system of administration, structure and organization, curricula, and teacher training in Algeria. Statistics provided by the Unesco Office of Statistics show enrollment at all…

Traffic Profiling in Wireless Sensor Networks

DTIC Science & Technology

2006-12-01

components, that can be used for traffic profiling and monitoring of a wireless sensor network . The work demostrates how the IDS should capture and...observed and analyzed. Finally, initial indications from basic analysis of wireless sensor network traffic demonstrated a high degree of self-similarity.

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

PubMed Central

Chen, Erbao; Xu, Xiaojing

2018-01-01

Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation. PMID:29849630

Molecular Profiling of Malignant Pleural Effusion in Metastatic Non-Small-Cell Lung Carcinoma. The Effect of Preanalytical Factors.

PubMed

Carter, Jamal; Miller, James Adam; Feller-Kopman, David; Ettinger, David; Sidransky, David; Maleki, Zahra

2017-07-01

Non-small-cell lung cancer (NSCLC)-associated malignant pleural effusions (MPEs) are sometimes the only available specimens for molecular analysis. This study evaluates diagnostic yield of NSCLC-associated MPE, its adequacy for molecular profiling and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. Molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated. Molecular profiling was performed on cell blocks and consisted of fluorescent in situ hybridization (FISH) for ALK gene rearrangements and the following sequencing platforms: Sanger sequencing (for EGFR) and high-throughput pyrosequencing (for KRAS and BRAF) during the first 4 years of the study period, and targeted next-generation sequencing performed thereafter. A total of 50 NSCLC-associated MPE cases were identified where molecular testing was requested. Of these, 17 cases were excluded: 14 cases (28%) due to inadequate tumor cellularity and 3 cases due to unavailability of the slides to review. A total of 27 out of 50 MPE cases (54%) underwent at least EGFR and KRAS sequencing and FISH for ALK rearrangement. Of the 27 cases with molecular testing results available, a genetic abnormality was detected in 16 cases (59%). The most common genetic aberrations identified involved EGFR ( 9 ) and KRAS ( 7 ). Six cases had ALK FISH only, of which one showed rearrangement. MPE volume was not associated with overall cellularity or tumor cellularity (P = 0.360). Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in 59% of samples with minimal risk of false negative.

Simulation of stimuli-triggered release of molecular species from halloysite nanotubes

NASA Astrophysics Data System (ADS)

Elumalai, Divya Narayan; Tully, Joshua; Lvov, Yuri; Derosa, Pedro A.

2016-10-01

A Monte Carlo model is used to study the effect of environmental variables (pH and temperature) on the transport and release of dexamethasone molecules from Halloysite Nanotubes (HNTs) in a dielectric fluid medium. The model used for this study was introduced elsewhere and it is based on basic physics interactions without experimental parameters for these interactions. An intermediate phase between the burst and saturation phase is found and explained. Molecules experience a 1-D diffusion process that is different from the diffusion in the burst phase or the surface diffusion experienced by molecules attached to the wall. It is predicted that this phase exists when the molecule-wall interaction is attractive but not always noticeable in the release profile. In this work, it is shown that an agreement with the experiment better than previously reported is obtained when simulated delivery curves are produced by the weighted average of the release profiles from a collection of HNTs with diameters and lengths distributed according to the experimental sample, highlighting the relevance of HNTs' morphology in the release. HNTs are suitable for environment-triggered release and thus the effect of temperature, molecule zeta potential, and pH is studied. It is observed that for temperatures that significantly differ from room temperature (by 100's of degrees), the release profile changes significantly, increasing the delivery speed at high temperature and reducing that speed at low temperature. Finally, it is observed that as the pH becomes more acidic, both the molecule and inner wall surface become more positive (or less negative) with both eventually becoming positive leading to a repulsive interaction; thus, molecules are pushed out by electrostatic repulsion. On the contrary, as the pH becomes more basic, positive molecules become more positive while the wall becomes less negative, but even at pH 12, the wall remains negative and the interaction is attractive. Changes in pH between different regions may act as a trigger for delivery or as a control in the delivery rate.

Intergenerational Projects: Idea Book.

ERIC Educational Resources Information Center

Clay, Rebecca; Ventura-Merkel, Cathy; Eades-Goudy, Dianne; Dubich, Teresa

This book profiles 74 intergenerational programs in the United States. The programs range from basic tutoring projects to a sophisticated corporate-based day care center. Project selection was based on replicatable programs involving mutually beneficial exchanges. Grouped by subjects, profiles include programs targeting both young and old. Most…

Characterization of potential plasma biomarkers related to cognitive impairment by untargeted profiling of phospholipids using the HILIC-ESI-IT-TOF-MS system.

PubMed

Song, Shuang; Cheong, Ling-Zhi; Man, Qing-Qing; Pang, Shao-Jie; Li, Yue-Qi; Ren, Biao; Zhang, Jian

2018-05-01

Early diagnosis of neural changes causing cognitive impairment is critical for development of preventive therapies for dementia. Biomarkers currently characterized cannot be extensively applied due to the invasive sampling of cerebrospinal fluid. The other imaging approaches are either expensive or require a high technique. Phospholipids (PLs), which are basic constituents of neurons, might be a key variable in the pathogenesis of cognitive impairment. Changes in plasma PL provide the possibility for development of novel biomarkers with minimal invasion and high patient acceptance. In this work, a HILIC-ESI-IT-TOF-MS system was introduced for untargeted profiling of plasma PLs to investigate the relationship between changes of plasma PL profiles and cognitive impairment. A total of 272 types of PL molecular structures were characterized in human plasma and quantified through the internal standard method. Univariate analysis shows 29 PLs were significantly different between the control (n = 41) and the cognitive impairment (CI) group (n = 41). Multivariate analysis (PCA and OPLS-DA) was conducted based on these 29 potential PL biomarkers. Both univariate and multivariate analyses show abnormality of PL metabolism in the CI group, and the downregulation of ethanolamine plasmalogen (pPE) supply, especially those with PUFAs, in the circulation system should be strongly associated with neurodegeneration. A discriminative model was established with satisfied fit (R2) and prediction (Q2) abilities, and the classification test showed better recognition of the CI group than the control group indicating that this model of PL biomarkers could be used as indicators for screening of CI. Graphical abstract Characterization of potential plasma biomarkers related to cognitive impairment by untargeted profiling of phospholipids.

Molecular inimitability amongst tumors: implications for precision cancer medicine in the age of personalized oncology.

PubMed

Patel, Sandip P; Schwaederle, Maria; Daniels, Gregory A; Fanta, Paul T; Schwab, Richard B; Shimabukuro, Kelly A; Kesari, Santosh; Piccioni, David E; Bazhenova, Lyudmila A; Helsten, Teresa L; Lippman, Scott M; Parker, Barbara A; Kurzrock, Razelle

2015-10-20

Tumor sequencing has revolutionized oncology, allowing for detailed interrogation of the molecular underpinnings of cancer at an individual level. With this additional insight, it is increasingly apparent that not only do tumors vary within a sample (tumor heterogeneity), but also that each patient's individual tumor is a constellation of unique molecular aberrations that will require an equally unique personalized therapeutic regimen. We report here the results of 439 patients who underwent Clinical Laboratory Improvement Amendment (CLIA)-certified next generation sequencing (NGS) across histologies. Among these patients, 98.4% had a unique molecular profile, and aside from three primary brain tumor patients with a single genetic lesion (IDH1 R132H), no two patients within a given histology were molecularly identical. Additionally, two sets of patients had identical profiles consisting of two mutations in common and no other anomalies. However, these profiles did not segregate by histology (lung adenocarcinoma-appendiceal cancer (KRAS G12D and GNAS R201C), and lung adenocarcinoma-liposarcoma (CDK4 and MDM2 amplification pairs)). These findings suggest that most advanced tumors are molecular singletons within and between histologies, and that tumors that differ in histology may still nonetheless exhibit identical molecular portraits, albeit rarely.

Molecular Cloning and Analysis of a DNA Repetitive Element from the Mouse Genome

ERIC Educational Resources Information Center

Geisinger, Adriana; Cossio, Gabriela; Wettstein, Rodolfo

2006-01-01

We report the development of a 3-week laboratory activity for an undergraduate molecular biology course. This activity introduces students to the practice of basic molecular techniques such as restriction enzyme digestion, agarose gel electrophoresis, cloning, plasmid DNA purification, Southern blotting, and sequencing. Students learn how to carry…

Assessment of Knowledge of Participants on Basic Molecular Biology Techniques after 5-Day Intensive Molecular Biology Training Workshops in Nigeria

ERIC Educational Resources Information Center

Yisau, J. I.; Adagbada, A. O.; Bamidele, T.; Fowora, M.; Brai, B. I. C.; Adebesin, O.; Bamidele, M.; Fesobi, T.; Nwaokorie, F. O.; Ajayi, A.; Smith, S. I.

2017-01-01

The deployment of molecular biology techniques for diagnosis and research in Nigeria is faced with a number of challenges, including the cost of equipment and reagents coupled with the dearth of personnel skilled in the procedures and handling of equipment. Short molecular biology training workshops were conducted at the Nigerian Institute of…

A Comprehensive Experiment for Molecular Biology: Determination of Single Nucleotide Polymorphism in Human REV3 Gene Using PCR-RFLP

ERIC Educational Resources Information Center

Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

2017-01-01

Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of…

Modern Spectroscopy

ERIC Educational Resources Information Center

Barrow, Gordon M.

1970-01-01

Presents the basic ideas of modern spectroscopy. Both the angular momenta and wave-nature approaches to the determination of energy level patterns for atomic and molecular systems are discussed. The interpretation of spectra, based on atomic and molecular models, is considered. (LC)

Training New Technologists in the Basics of Molecular Pathology.

ERIC Educational Resources Information Center

Matta, Nahida

1993-01-01

Outlines a training model designed to help senior technologists ensure that the newly hired technologists in the clinical molecular pathology laboratory achieve the minimum level of knowledge needed to perform and progress on the job. (Author)

Cancer Core Europe: a consortium to address the cancer care-cancer research continuum challenge.

PubMed

Eggermont, Alexander M M; Caldas, Carlos; Ringborg, Ulrik; Medema, René; Tabernero, Josep; Wiestler, Otmar

2014-11-01

European cancer research for a transformative initiative by creating a consortium of six leading excellent comprehensive cancer centres that will work together to address the cancer care-cancer research continuum. Prerequisites for joint translational and clinical research programs are very demanding. These require the creation of a virtual single 'e-hospital' and a powerful translational platform, inter-compatible clinical molecular profiling laboratories with a robust underlying computational biology pipeline, standardised functional and molecular imaging, commonly agreed Standard Operating Procedures (SOPs) for liquid and tissue biopsy procurement, storage and processing, for molecular diagnostics, 'omics', functional genetics, immune-monitoring and other assessments. Importantly also it requires a culture of data collection and data storage that provides complete longitudinal data sets to allow for: effective data sharing and common database building, and to achieve a level of completeness of data that is required for conducting outcome research, taking into account our current understanding of cancers as communities of evolving clones. Cutting edge basic research and technology development serve as an important driving force for innovative translational and clinical studies. Given the excellent track records of the six participants in these areas, Cancer Core Europe will be able to support the full spectrum of research required to address the cancer research- cancer care continuum. Cancer Core Europe also constitutes a unique environment to train the next generation of talents in innovative translational and clinical oncology. Copyright © 2014. Published by Elsevier Ltd.

Rapid identification and validation of novel targeted approaches for Glioblastoma: A combined ex vivo-in vivo pharmaco-omic model.

PubMed

Daher, Ahmad; de Groot, John

2018-01-01

Tumor heterogeneity is a major factor in glioblastoma's poor response to therapy and seemingly inevitable recurrence. Only two glioblastoma drugs have received Food and Drug Administration approval since 1998, highlighting the urgent need for new therapies. Profiling "omics" analyses have helped characterize glioblastoma molecularly and have thus identified multiple molecular targets for precision medicine. These molecular targets have influenced clinical trial design; many "actionable" mutation-focused trials are underway, but because they have not yet led to therapeutic breakthroughs, new strategies for treating glioblastoma, especially those with a pharmacological functional component, remain in high demand. In that regard, high-throughput screening that allows for expedited preclinical drug testing and the use of GBM models that represent tumor heterogeneity more accurately than traditional cancer cell lines is necessary to maximize the successful translation of agents into the clinic. High-throughput screening has been successfully used in the testing, discovery, and validation of potential therapeutics in various cancer models, but it has not been extensively utilized in glioblastoma models. In this report, we describe the basic aspects of high-throughput screening and propose a modified high-throughput screening model in which ex vivo and in vivo drug testing is complemented by post-screening pharmacological, pan-omic analysis to expedite anti-glioma drugs' preclinical testing and develop predictive biomarker datasets that can aid in personalizing glioblastoma therapy and inform clinical trial design. Copyright © 2017 Elsevier Inc. All rights reserved.

Rapid Sequential in Situ Multiplexing with DNA Exchange Imaging in Neuronal Cells and Tissues.

PubMed

Wang, Yu; Woehrstein, Johannes B; Donoghue, Noah; Dai, Mingjie; Avendaño, Maier S; Schackmann, Ron C J; Zoeller, Jason J; Wang, Shan Shan H; Tillberg, Paul W; Park, Demian; Lapan, Sylvain W; Boyden, Edward S; Brugge, Joan S; Kaeser, Pascal S; Church, George M; Agasti, Sarit S; Jungmann, Ralf; Yin, Peng

2017-10-11

To decipher the molecular mechanisms of biological function, it is critical to map the molecular composition of individual cells or even more importantly tissue samples in the context of their biological environment in situ. Immunofluorescence (IF) provides specific labeling for molecular profiling. However, conventional IF methods have finite multiplexing capabilities due to spectral overlap of the fluorophores. Various sequential imaging methods have been developed to circumvent this spectral limit but are not widely adopted due to the common limitation of requiring multirounds of slow (typically over 2 h at room temperature to overnight at 4 °C in practice) immunostaining. We present here a practical and robust method, which we call DNA Exchange Imaging (DEI), for rapid in situ spectrally unlimited multiplexing. This technique overcomes speed restrictions by allowing for single-round immunostaining with DNA-barcoded antibodies, followed by rapid (less than 10 min) buffer exchange of fluorophore-bearing DNA imager strands. The programmability of DEI allows us to apply it to diverse microscopy platforms (with Exchange Confocal, Exchange-SIM, Exchange-STED, and Exchange-PAINT demonstrated here) at multiple desired resolution scales (from ∼300 nm down to sub-20 nm). We optimized and validated the use of DEI in complex biological samples, including primary neuron cultures and tissue sections. These results collectively suggest DNA exchange as a versatile, practical platform for rapid, highly multiplexed in situ imaging, potentially enabling new applications ranging from basic science, to drug discovery, and to clinical pathology.

Binding affinity of pro-apoptotic BH3 peptides for the anti-apoptotic Mcl-1 and A1 proteins: Molecular dynamics simulations of Mcl-1 and A1 in complex with six different BH3 peptides.

PubMed

Modi, Vivek; Sankararamakrishnan, Ramasubbu

2017-05-01

The anti-apoptotic members of Bcl-2 family of proteins bind to their pro-apoptotic counterparts to induce or prevent cell death.Based on the distinct binding profiles for specific pro-apoptotic BH3 peptides, the anti-apoptotic Bcl-2 proteins can be divided into at least two subclasses. The subclass that includes Bcl-X L binds strongly to Bad BH3 peptide while it has weak binding affinity for the second subclass of Bcl-2 proteins such as Mcl-1 and A1. Anti-apoptotic Bcl-2 proteins are considered to be attractive drug targets for anti-cancer drugs. BH3-mimetic inhibitors such as ABT-737 have been shown to be specific to Bcl-X L subclass while Mcl-1 and A1 show resistance to the same drug. An efficacious inhibitor should target all the anti-apoptotic Bcl-2 proteins. Hence, development of inhibitors selective to Mcl-1 and A1 is of prime importance for targeted cancer therapeutics. The first step to achieve this goal is to understand the molecular basis of high binding affinities of specific pro-apoptotic BH3 peptides for Mcl-1 and A1. To understand the interactions between the BH3 peptides and Mcl-1/A1, we performed multi-nanosecond molecular dynamics (MD) simulations of six complex structures of Mcl-1 and A1. With the exception of Bad, all complex structures were experimentally determined. Bad complex structures were modeled. Our simulation studies identified specific pattern of polar interactions between Mcl-1/A1 and high-affinity binding BH3 peptides. The lack of such polar interactions in Bad peptide complex is attributed to specific basic residues present before and after the highly conserved Leu residue. The close approach of basic residues in Bad and Mcl-1/A1 is hypothesized to be the cause of weak binding affinity. To test this hypothesis, we generated in silico mutants of these basic residues in Bad peptide and Mcl-1/A1 proteins. MD simulations of the mutant systems established the pattern of stable polar interactions observed in high-affinity binding BH3 peptides. We have thus identified specific residue positions in Bad and Mcl-1/A1 responsible for the weak binding affinity. Results from these simulation studies will aid in the development of inhibitors specific to Mcl-1 and A1 proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence for the importance of personalized molecular profiling in pancreatic cancer.

PubMed

Lili, Loukia N; Matyunina, Lilya V; Walker, L DeEtte; Daneker, George W; McDonald, John F

2014-03-01

There is a growing body of evidence that targeted gene therapy holds great promise for the future treatment of cancer. A crucial step in this therapy is the accurate identification of appropriate candidate genes/pathways for targeted treatment. One approach is to identify variant genes/pathways that are significantly enriched in groups of afflicted individuals relative to control subjects. However, if there are multiple molecular pathways to the same cancer, the molecular determinants of the disease may be heterogeneous among individuals and possibly go undetected by group analyses. In an effort to explore this question in pancreatic cancer, we compared the most significantly differentially expressed genes/pathways between cancer and control patient samples as determined by group versus personalized analyses. We found little to no overlap between genes/pathways identified by gene expression profiling using group analyses relative to those identified by personalized analyses. Our results indicate that personalized and not group molecular profiling is the most appropriate approach for the identification of putative candidates for targeted gene therapy of pancreatic and perhaps other cancers with heterogeneous molecular etiology.

The Cancer Genome Atlas Pan-Cancer analysis project.

PubMed

Weinstein, John N; Collisson, Eric A; Mills, Gordon B; Shaw, Kenna R Mills; Ozenberger, Brad A; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M

2013-10-01

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

Safe and Secure Services Based on NGN

NASA Astrophysics Data System (ADS)

Fukazawa, Tomoo; Nisase, Takemi; Kawashima, Masahisa; Hariu, Takeo; Oshima, Yoshihito

Next Generation Network (NGN), which has been undergoing standardization as it has developed, is expected to create new services that converge the fixed and mobile networks. This paper introduces the basic requirements for NGN in terms of security and explains the standardization activities, in particular, the requirements for the security function described in Y.2701 discussed in ITU-T SG-13. In addition to the basic NGN security function, requirements for NGN authentication are also described from three aspects: security, deployability, and service. As examples of authentication implementation, three profiles-namely, fixed, nomadic, and mobile-are defined in this paper. That is, the “fixed profile” is typically for fixed-line subscribers, the “nomadic profile” basically utilizes WiFi access points, and the “mobile profile” provides ideal NGN mobility for mobile subscribers. All three of these profiles satisfy the requirements from security aspects. The three profiles are compared from the viewpoint of requirements for deployability and service. After showing that none of the three profiles can fulfill all of the requirements, we propose that multiple profiles should be used by NGN providers. As service and application examples, two promising NGN applications are proposed. The first is a strong authentication mechanism that makes Web applications more safe and secure even against password theft. It is based on NGN ID federation function. The second provides an easy peer-to-peer broadband virtual private network service aimed at safe and secure communication for personal/SOHO (small office, home office) users, based on NGN SIP (session initiation protocol) session control.

Prescriptive Profile Procedure for Children With Learning Disabilities.

ERIC Educational Resources Information Center

Levine, Eleanor; Fineman, Carol

The Prescriptive Profile Procedure (PPP) attempts to provide teachers of learning disabled elementary school children with a procedure of individualized diagnosis and educational prescription which encompasses strengths and weaknesses in prerequisite skills, basic school subjects, and behavioral factors. A competency statement and six to 12…

Quantifying and Interpreting Group Differences in Interest Profiles

ERIC Educational Resources Information Center

Armstrong, Patrick Ian; Fouad, Nadya A.; Rounds, James; Hubert, Lawrence

2010-01-01

Research on group differences in interests has often focused on structural hypotheses and mean-score differences in Holland's (1997) theory, with comparatively little research on basic interest measures. Group differences in interest profiles were examined using statistical methods for matching individuals with occupations, the C-index, Q…

Bringing ayahuasca to the clinical research laboratory.

PubMed

Riba, Jordi; Barbanoj, Manel J

2005-06-01

Since the winter of 1999, the authors and their research team have been conducting clinical studies involving the administration of ayahuasca to healthy volunteers. The rationale for conducting this kind of research is twofold. First, the growing interest of many individuals for traditional indigenous practices involving the ingestion of natural psychotropic drugs such as ayahuasca demands the systematic study of their pharmacological profiles in the target species, i.e., human beings. The complex nature of ayahuasca brews combining a large number of pharmacologically active compounds requires that research be carried out to establish the safety and overall pharmacological profile of these products. Second, the authors believe that the study of psychedelics in general calls for renewed attention. Although the molecular and electrophysiological level effects of these drugs are relatively well characterized, current knowledge of the mechanisms by which these compounds modify the higher order cognitive processes in the way they do is still incomplete, to say the least. The present article describes the development of the research effort carried out at the Autonomous University of Barcelona, commenting on several methodological aspects and reviewing the basic clinical findings. It also describes the research currently underway in our laboratory, and briefly comments on two new studies we plan to undertake in order to further our knowledge of the pharmacology of ayahuasca.

System analysis identifies distinct and common functional networks governed by transcription factor ASCL1, in glioma and small cell lung cancer.

PubMed

Donakonda, Sainitin; Sinha, Swati; Dighe, Shrinivas Nivrutti; Rao, Manchanahalli R Satyanarayana

2017-07-25

ASCL1 is a basic Helix-Loop-Helix transcription factor (TF), which is involved in various cellular processes like neuronal development and signaling pathways. Transcriptome profiling has shown that ASCL1 overexpression plays an important role in the development of glioma and Small Cell Lung Carcinoma (SCLC), but distinct and common molecular mechanisms regulated by ASCL1 in these cancers are unknown. In order to understand how it drives the cellular functional network in these two tumors, we generated a gene expression profile in a glioma cell line (U87MG) to identify ASCL1 gene targets by an si RNA silencing approach and then compared this with a publicly available dataset of similarly silenced SCLC (NCI-H1618 cells). We constructed TF-TF and gene-gene interactions, as well as protein interaction networks of ASCL1 regulated genes in glioma and SCLC cells. Detailed network analysis uncovered various biological processes governed by ASCL1 target genes in these two tumor cell lines. We find that novel ASCL1 functions related to mitosis and signaling pathways influencing development and tumor growth are affected in both glioma and SCLC cells. In addition, we also observed ASCL1 governed functional networks that are distinct to glioma and SCLC.

Methylation and expression profiles of MGMT gene in thymic epithelial tumors.

PubMed

Mokhtar, Mohamed; Kondo, Kazuya; Namura, Toshiaki; Ali, Abdellah H K; Fujita, Yui; Takai, Chikako; Takizawa, Hiromitsu; Nakagawa, Yasushi; Toba, Hiroaki; Kajiura, Koichiro; Yoshida, Mitsuteru; Kawakami, Gyokei; Sakiyama, Shoji; Tangoku, Akira

2014-02-01

A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Molecular filter-based diagnostics in high speed flows

NASA Technical Reports Server (NTRS)

Elliott, Gregory S.; Samimy, MO; Arnette, Stephen A.

1993-01-01

The use of iodine molecular filters in nonintrusive planar velocimetry methods is examined. Detailed absorption profiles are obtained to highlight the effects that determine the profile shape. It is shown that pressure broadening induced by the presence of a nonabsorbing vapor can be utilized to significantly change the slopes bounding the absorbing region while remaining in the optically-thick regime.

Electron momentum spectroscopy of dimethyl ether taking account of nuclear dynamics in the electronic ground state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morini, Filippo; Deleuze, Michael Simon, E-mail: michael.deleuze@uhasselt.be; Watanabe, Noboru

The influence of nuclear dynamics in the electronic ground state on the (e,2e) momentum profiles of dimethyl ether has been analyzed using the harmonic analytical quantum mechanical and Born-Oppenheimer molecular dynamics approaches. In spite of fundamental methodological differences, results obtained with both approaches consistently demonstrate that molecular vibrations in the electronic ground state have a most appreciable influence on the momentum profiles associated to the 2b{sub 1}, 6a{sub 1}, 4b{sub 2}, and 1a{sub 2} orbitals. Taking this influence into account considerably improves the agreement between theoretical and newly obtained experimental momentum profiles, with improved statistical accuracy. Both approaches point outmore » in particular the most appreciable role which is played by a few specific molecular vibrations of A{sub 1}, B{sub 1}, and B{sub 2} symmetries, which correspond to C–H stretching and H–C–H bending modes. In line with the Herzberg-Teller principle, the influence of these molecular vibrations on the computed momentum profiles can be unraveled from considerations on the symmetry characteristics of orbitals and their energy spacing.« less

Molecular profiling of single circulating tumor cells from lung cancer patients.

PubMed

Park, Seung-Min; Wong, Dawson J; Ooi, Chin Chun; Kurtz, David M; Vermesh, Ophir; Aalipour, Amin; Suh, Susie; Pian, Kelsey L; Chabon, Jacob J; Lee, Sang Hun; Jamali, Mehran; Say, Carmen; Carter, Justin N; Lee, Luke P; Kuschner, Ware G; Schwartz, Erich J; Shrager, Joseph B; Neal, Joel W; Wakelee, Heather A; Diehn, Maximilian; Nair, Viswam S; Wang, Shan X; Gambhir, Sanjiv S

2016-12-27

Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.

Understanding molecular structure from molecular mechanics.

PubMed

Allinger, Norman L

2011-04-01

Molecular mechanics gives us a well known model of molecular structure. It is less widely recognized that valence bond theory gives us structures which offer a direct interpretation of molecular mechanics formulations and parameters. The electronic effects well-known in physical organic chemistry can be directly interpreted in terms of valence bond structures, and hence quantitatively calculated and understood. The basic theory is outlined in this paper, and examples of the effects, and their interpretation in illustrative examples is presented.

Electrostatic potential profiles of molecular conductors

NASA Astrophysics Data System (ADS)

Liang, G. C.; Ghosh, A. W.; Paulsson, M.; Datta, S.

2004-03-01

The electrostatic potential across a short ballistic molecular conductor depends sensitively on the geometry of its environment, and can affect its conduction significantly by influencing its energy levels and wave functions. We illustrate some of the issues involved by evaluating the potential profiles for a conducting gold wire and an aromatic phenyl dithiol molecule in various geometries. The potential profile is obtained by solving Poisson’s equation with boundary conditions set by the contact electrochemical potentials and coupling the result self-consistently with a nonequilibrium Green’s function formulation of transport. The overall shape of the potential profile (ramp versus flat) depends on the feasibility of transverse screening of electric fields. Accordingly, the screening is better for a thick wire, a multiwalled nanotube, or a close-packed self-assembled monolayer, in comparison to a thin wire, a single-walled nanotube, or an isolated molecular conductor. The electrostatic potential further governs the alignment or misalignment of intramolecular levels, which can strongly influence the molecular current voltage (I V) characteristic. An external gate voltage can modify the overall potential profile, changing the I V characteristic from a resonant conducting to a saturating one. The degree of saturation and gate modulation depends on the availability of metal-induced-gap states and on the electrostatic gate control parameter set by the ratio of the gate oxide thickness to the channel length.

Investigation of Salmonella Enteritidis outbreaks in South Africa using multi-locus variable-number tandem-repeats analysis, 2013-2015.

PubMed

Muvhali, Munyadziwa; Smith, Anthony Marius; Rakgantso, Andronica Moipone; Keddy, Karen Helena

2017-10-02

Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) has become a significant pathogen in South Africa, and the need for improved molecular surveillance of this pathogen has become important. Over the years, multi-locus variable-number tandem-repeats analysis (MLVA) has become a valuable molecular subtyping technique for Salmonella, particularly for highly homogenic serotypes such as Salmonella Enteritidis. This study describes the use of MLVA in the molecular epidemiological investigation of outbreak isolates in South Africa. Between the years 2013 and 2015, the Centre for Enteric Diseases (CED) received 39 Salmonella Enteritidis isolates from seven foodborne illness outbreaks, which occurred in six provinces. MLVA was performed on all isolates. Three MLVA profiles (MLVA profiles 21, 22 and 28) were identified among the 39 isolates. MLVA profile 28 accounted for 77% (30/39) of the isolates. Isolates from a single outbreak were grouped into a single MLVA profile. A minimum spanning tree (MST) created from the MLVA data showed a close relationship between MLVA profiles 21, 22 and 28, with a single VNTR locus difference between them. MLVA has proven to be a reliable method for the molecular epidemiological investigation of Salmonella Enteritidis outbreaks in South Africa. These foodborne outbreaks emphasize the importance of the One Health approach as an essential component for combating the spread of zoonotic pathogens such as Salmonella Enteritidis.

Theranostic Profiling for Actionable Aberrations in Advanced High Risk Osteosarcoma with Aggressive Biology Reveals High Molecular Diversity: The Human Fingerprint Hypothesis.

PubMed

Egas-Bejar, Daniela; Anderson, Pete M; Agarwal, Rishi; Corrales-Medina, Fernando; Devarajan, Eswaran; Huh, Winston W; Brown, Robert E; Subbiah, Vivek

2014-03-12

The survival of patients with advanced osteosarcoma is poor with limited therapeutic options. There is an urgent need for new targeted therapies based on biomarkers. Recently, theranostic molecular profiling services for cancer patients by CLIA-certified commercial companies as well as in-house profiling in academic medical centers have expanded exponentially. We evaluated molecular profiles of patients with advanced osteosarcoma whose tumor tissue had been analyzed by one of the following methods: 1. 182-gene next-generation exome sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/PCR-based panel (CARIS Target Now, Irving, Tx), 3.Comparative genome hybridization (Oncopath, San Antonio, TX). 4. Single-gene PCR assays, PTEN IHC (MDACC CLIA), 5. UT Houston morphoproteomics (Houston, TX). The most common actionable aberrations occur in the PI3K/PTEN/mTOR pathway. No patterns in genomic alterations beyond the above are readily identifiable, and suggest both high molecular diversity in osteosarcoma and the need for more analyses to define distinct subgroups of osteosarcoma defined by genomic alterations. Based on our preliminary observations we hypothesize that the biology of aggressive and the metastatic phenotype osteosarcoma at the molecular level is similar to human fingerprints, in that no two tumors are identical. Further large scale analyses of osteosarcoma samples are warranted to test this hypothesis.

Molecular Diagnostics of the Internal Structure of Starspots and Sunspots

NASA Astrophysics Data System (ADS)

Afram, N.; Berdyugina, S. V.; Fluri, D. M.; Solanki, S. K.; Lagg, A.; Petit, P.; Arnaud, J.

2006-12-01

We have analyzed the usefulness of molecules as a diagnostic tool for studying solar and stellar magnetism with the molecular Zeeman and Paschen-Back effects. In the first part we concentrate on molecules that are observed in sunspots such as MgH and TiO. We present calculated molecular line profiles obtained by assuming magnetic fields of 2-3 kG and compare these synthetic Stokes profiles with spectro-polarimetric observations in sunspots. The good agreement between the theory and observations allows us to turn our attention in the second part to starspots to gain insight into their internal structure. We investigate the temperature range in which the selected molecules can serve as indicators for magnetic fields on highly active cool stars and compare synthetic Stokes profiles with our recent observations.

The Transition from Mathematician to Astrophysicist

NASA Astrophysics Data System (ADS)

Flannery, M. R.

Various landmarks in the evolution of Alexander Dalgarno from a gifted mathematician to becoming the acknowledged Father of Molecular Astrophysics are noted. His researches in basic atomic and molecular physics, aeronomy (the study of the upper atmosphere) and astrophysics are highlighted.

Validation of the Military Entrance Physical Strength Capacity Test. Technical Report 610.

ERIC Educational Resources Information Center

Myers, David C.; And Others

A battery of physical ability tests was validated using a predictive, criterion-related strategy. The battery was given to 1,003 female soldiers and 980 male soldiers before they had begun Army Basic Training. Criterion measures which represented physical competency in Basic Training (physical proficiency tests, sick call, profiles, and separation…

Fundamentals of Welding. Teacher Edition [and] Student Edition [and] Student Workbook. Second Edition.

ERIC Educational Resources Information Center

Fortney, Clarence; Gregory, Mike; New, Larry

Teacher and student editions and a student workbook for fundamentals of welding comprise the first of six in a series of competency-based instructional materials for welding programs. Introductory pages in the teacher edition are training and competency profile, instructional/task analysis, basic skills icons and classifications, basic skills…

Illinois Adult Literacy Failing the Workforce: Alternative Solution Needed. Policy Profiles.

ERIC Educational Resources Information Center

Banovetz, James M., Ed.

According to the most recent National Adult Literacy Survey, nearly half of Illinois adults lack sufficient reading proficiency to ensure job success and advancement in 21st century workplaces. The Test of Adult Basic Education is currently used as a pretest/posttest in Illinois' existing adult basic education, adult secondary education, and…

Predicting solute partitioning in lipid bilayers: Free energies and partition coefficients from molecular dynamics simulations and COSMOmic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobtorweihen, S., E-mail: jakobtorweihen@tuhh.de; Ingram, T.; Gerlach, T.

2014-07-28

Quantitative predictions of biomembrane/water partition coefficients are important, as they are a key property in pharmaceutical applications and toxicological studies. Molecular dynamics (MD) simulations are used to calculate free energy profiles for different solutes in lipid bilayers. How to calculate partition coefficients from these profiles is discussed in detail and different definitions of partition coefficients are compared. Importantly, it is shown that the calculated coefficients are in quantitative agreement with experimental results. Furthermore, we compare free energy profiles from MD simulations to profiles obtained by the recent method COSMOmic, which is an extension of the conductor-like screening model for realisticmore » solvation to micelles and biomembranes. The free energy profiles from these molecular methods are in good agreement. Additionally, solute orientations calculated with MD and COSMOmic are compared and again a good agreement is found. Four different solutes are investigated in detail: 4-ethylphenol, propanol, 5-phenylvaleric acid, and dibenz[a,h]anthracene, whereby the latter belongs to the class of polycyclic aromatic hydrocarbons. The convergence of the free energy profiles from biased MD simulations is discussed and the results are shown to be comparable to equilibrium MD simulations. For 5-phenylvaleric acid the influence of the carboxyl group dihedral angle on free energy profiles is analyzed with MD simulations.« less

Molecular dynamic simulation of Ar-Kr mixture across a rough walled nanochannel: Velocity and temperature profiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pooja,, E-mail: pupooja16@gmail.com; Ahluwalia, P. K., E-mail: pk-ahluwalia7@yahoo.com; Pathania, Y.

2015-05-15

This paper presents the results from a molecular dynamics simulation of mixture of argon and krypton in the Poiseuille flow across a rough walled nanochannel. The roughness effect on liquid nanoflows has recently drawn attention The computational software used for carrying out the molecular dynamics simulations is LAMMPS. The fluid flow takes place between two parallel plates and is bounded by horizontal rough walls in one direction and periodic boundary conditions are imposed in the other two directions. Each fluid atom interacts with other fluid atoms and wall atoms through Leenard-Jones (LJ) potential with a cut off distance of 5.0.more » To derive the flow a constant force is applied whose value is varied from 0.1 to 0.3 and velocity profiles and temperature profiles are noted for these values of forces. The velocity profile and temperature profiles are also looked at different channel widths of nanochannel and at different densities of mixture. The velocity profile and temperature profile of rough walled nanochannel are compared with that of smooth walled nanochannel and it is concluded that mean velocity increases with increase in channel width, force applied and decrease in density also with introduction of roughness in the walls of nanochannel mean velocity again increases and results also agree with the analytical solution of a Poiseuille flow.« less

Molecular dynamic simulation of Ar-Kr mixture across a rough walled nanochannel: Velocity & temperature profiles

NASA Astrophysics Data System (ADS)

Pooja, Pathania, Y.; Ahluwalia, P. K.

2015-05-01

This paper presents the results from a molecular dynamics simulation of mixture of argon and krypton in the Poiseuille flow across a rough walled nanochannel. The roughness effect on liquid nanoflows has recently drawn attention The computational software used for carrying out the molecular dynamics simulations is LAMMPS. The fluid flow takes place between two parallel plates and is bounded by horizontal rough walls in one direction and periodic boundary conditions are imposed in the other two directions. Each fluid atom interacts with other fluid atoms and wall atoms through Leenard-Jones (LJ) potential with a cut off distance of 5.0. To derive the flow a constant force is applied whose value is varied from 0.1 to 0.3 and velocity profiles and temperature profiles are noted for these values of forces. The velocity profile and temperature profiles are also looked at different channel widths of nanochannel and at different densities of mixture. The velocity profile and temperature profile of rough walled nanochannel are compared with that of smooth walled nanochannel and it is concluded that mean velocity increases with increase in channel width, force applied and decrease in density also with introduction of roughness in the walls of nanochannel mean velocity again increases and results also agree with the analytical solution of a Poiseuille flow.

Demonstration of the Principles of Restriction Endonuclease Cleavage Reactions Using Thermostable Bfl I from "Anoxybacillus Flavithermus"

ERIC Educational Resources Information Center

Sharma, Prince; D'Souza, David R.; Bhandari, Deepali; Parashar, Vijay; Capalash, Neena

2003-01-01

Restriction enzymes are basic tools in recombinant DNA technology. To shape the molecular biology experiments, the students must know how to work with these molecular scissors. Here, we describe an integrated set of experiments, introduced in the "Advances in Molecular Biology and Biotechnology" postgraduate course, which covers the important…

Molecular classification of fatty liver by high-throughput profiling of protein post-translational modifications.

PubMed

Urasaki, Yasuyo; Fiscus, Ronald R; Le, Thuc T

2016-04-01

We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Perfect Composition Depth Profiling of Ionic Liquid Surfaces Using High-resolution RBS/ERDA.

PubMed

Nakajima, Kaoru; Zolboo, Enkhbayar; Ohashi, Tomohiro; Lísal, Martin; Kimura, Kenji

2016-01-01

In order to reveal the surface structures of large molecular ionic liquids (ILs), the near-surface elemental depth distributions of 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C n C 1 Im][Tf 2 N], n = 2, 6, 10) were studied using high-resolution Rutherford backscattering spectroscopy (HRBS) in combination with high-resolution elastic recoil detection analysis (HR-ERDA). The elemental depth profiles of all constituent elements, including hydrogen, were derived from HR-ERDA/HRBS measurements, so that the profiles would reproduce both HR-ERDA and HRBS spectra simultaneously. The derived elemental depth profiles agree with state-of-the-art molecular dynamics simulations, indicating the feasibility of this method. A controversy concerning the preferential orientation of [C 2 C 1 Im] at the surface has been resolved by this new combination analysis; namely, the [C 2 C 1 Im] cation has a preferential orientation with the ethyl chain pointing towards the vacuum in the topmost molecular layer.

Culinary Arts Profile.

ERIC Educational Resources Information Center

Missouri Univ., Columbia. Instructional Materials Lab.

This chart is intended for use in documenting the fact that a student participating in a culinary arts program has achieved the performance standards specified in the Missouri Competency Profile for culinary arts. The chart includes space for recording basic student and instructor information and the student's on-the-job training and work…

Ego-Stage Development and Interaction.

ERIC Educational Resources Information Center

Fay, Francis Anderson

The principal aim of the study was to determine whether, in the verbal interaction in a group of nine adults engaged in adult education, a systematic relationship could be shown between members' ego-stage profiles and their patterns of participation. Active ego-stage profiles were constructed of basic ego identity concerns using Erikson's…

A Comprehensive Examination of Reading Heterogeneity in Students with High Functioning Autism: Distinct Reading Profiles and Their Relation to Autism Symptom Severity

ERIC Educational Resources Information Center

McIntyre, Nancy S.; Solari, Emily J.; Grimm, Ryan P.; E. Lerro, Lindsay; E. Gonzales, Joseph; Mundy, Peter C.

2017-01-01

The goal of this study was to identify unique profiles of readers in a sample of 8-16 year olds with higher functioning autism spectrum disorders (HFASD) and examine the profiles in relation to ASD symptom severity. Eighty-one students were assessed utilizing a comprehensive reading battery that included basic word reading, language, and…

A Comprehensive Examination of Reading Heterogeneity in Students with High Functioning Autism: Distinct Reading Profiles and Their Relations to Autism Symptom Severity

ERIC Educational Resources Information Center

McIntyre, Nancy S.; Solari, Emily J.; Grimm, Ryan P.; Lerro, Lindsay E.; Gonzalez, Joseph E.; Mundy, Peter C.

2017-01-01

The goal of this study was to identify unique profiles of readers in a sample of 8-16 year olds with higher functioning autism spectrum disorders (HFASD) and examine the profiles in relation to ASD symptom severity. Eighty-one students were assessed utilizing a comprehensive reading battery that included basic word reading, language, and…

Concomitant prediction of function and fold at the domain level with GO-based profiles.

PubMed

Lopez, Daniel; Pazos, Florencio

2013-01-01

Predicting the function of newly sequenced proteins is crucial due to the pace at which these raw sequences are being obtained. Almost all resources for predicting protein function assign functional terms to whole chains, and do not distinguish which particular domain is responsible for the allocated function. This is not a limitation of the methodologies themselves but it is due to the fact that in the databases of functional annotations these methods use for transferring functional terms to new proteins, these annotations are done on a whole-chain basis. Nevertheless, domains are the basic evolutionary and often functional units of proteins. In many cases, the domains of a protein chain have distinct molecular functions, independent from each other. For that reason resources with functional annotations at the domain level, as well as methodologies for predicting function for individual domains adapted to these resources are required.We present a methodology for predicting the molecular function of individual domains, based on a previously developed database of functional annotations at the domain level. The approach, which we show outperforms a standard method based on sequence searches in assigning function, concomitantly predicts the structural fold of the domains and can give hints on the functionally important residues associated to the predicted function.

Molecular characterization and expression analysis of three novel autophagy-related genes from the cattle tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

PubMed

Flores Fernández, José Miguel; Barragán Álvarez, Carla Patricia; Sánchez Hernández, Carla Vanessa; Padilla Camberos, Eduardo; González Castillo, Celia; Ortuño Sahagún, Daniel; Martínez Velázquez, Moisés

2016-11-01

The cattle tick Rhipicephalus (Boophilus) microplus is a hematophagous ectoparasite of major importance for the livestock industry. It shows a remarkable ability to survive over long periods without feeding. However, the mechanisms used to endure long-term starvation are poorly understood. It is believed that autophagy, a process of intracellular protein degradation, may play a significant role to confront adverse environmental conditions. To advance our understanding of autophagy in R. microplus, in the present study we report the molecular characterization of three autophagy-related (ATG) genes, namely, RmATG3, RmATG4 and RmATG6, as well as their expression profiles in different developmental stages and organs of the parasite. The deduced amino acid sequences derived from the characterized gene sequences were subjected to Basic Local Alignment Search Tool analysis. The testing produced significant alignments with respective ATG proteins from Haemaphysalis longicornis and Ixodes scapularis ticks. Real-time polymerase chain reaction assays revealed that RmATG4 and RmATG6 transcripts were elevated in egg and ovary tissue, when compared with larva and midgut samples, while RmATG3 expression in midgut was 2-fold higher than in egg, larva and ovary samples.

Comparisons between tokamak fueling of gas puffing and supersonic molecular beam injection in 2D simulations

DOE PAGES

Zhou, Y. L.; Wang, Z. H.; Xu, X. Q.; ...

2015-01-09

Plasma fueling with high efficiency and deep injection is very important to enable fusion power performance requirements. It is a powerful and efficient way to study neutral transport dynamics and find methods of improving the fueling performance by doing large scale simulations. Furthermore, two basic fueling methods, gas puffing (GP) and supersonic molecular beam injection (SMBI), are simulated and compared in realistic divertor geometry of the HL-2A tokamak with a newly developed module, named trans-neut, within the framework of BOUT++ boundary plasma turbulence code [Z. H. Wang et al., Nucl. Fusion 54, 043019 (2014)]. The physical model includes plasma density,more » heat and momentum transport equations along with neutral density, and momentum transport equations. In transport dynamics and profile evolutions of both plasma and neutrals are simulated and compared between GP and SMBI in both poloidal and radial directions, which are quite different from one and the other. It finds that the neutrals can penetrate about four centimeters inside the last closed (magnetic) flux surface during SMBI, while they are all deposited outside of the LCF during GP. Moreover, it is the radial convection and larger inflowing flux which lead to the deeper penetration depth of SMBI and higher fueling efficiency compared to GP.« less

Comparisons between tokamak fueling of gas puffing and supersonic molecular beam injection in 2D simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Y. L.; Wang, Z. H.; Xu, X. Q.

Plasma fueling with high efficiency and deep injection is very important to enable fusion power performance requirements. It is a powerful and efficient way to study neutral transport dynamics and find methods of improving the fueling performance by doing large scale simulations. Furthermore, two basic fueling methods, gas puffing (GP) and supersonic molecular beam injection (SMBI), are simulated and compared in realistic divertor geometry of the HL-2A tokamak with a newly developed module, named trans-neut, within the framework of BOUT++ boundary plasma turbulence code [Z. H. Wang et al., Nucl. Fusion 54, 043019 (2014)]. The physical model includes plasma density,more » heat and momentum transport equations along with neutral density, and momentum transport equations. In transport dynamics and profile evolutions of both plasma and neutrals are simulated and compared between GP and SMBI in both poloidal and radial directions, which are quite different from one and the other. It finds that the neutrals can penetrate about four centimeters inside the last closed (magnetic) flux surface during SMBI, while they are all deposited outside of the LCF during GP. Moreover, it is the radial convection and larger inflowing flux which lead to the deeper penetration depth of SMBI and higher fueling efficiency compared to GP.« less

Comparisons between tokamak fueling of gas puffing and supersonic molecular beam injection in 2D simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Y. L.; Southwestern Institute of Physics, Chengdu 610041; Wang, Z. H., E-mail: zhwang@swip.ac.cn

Plasma fueling with high efficiency and deep injection is very important to enable fusion power performance requirements. It is a powerful and efficient way to study neutral transport dynamics and find methods of improving the fueling performance by doing large scale simulations. Two basic fueling methods, gas puffing (GP) and supersonic molecular beam injection (SMBI), are simulated and compared in realistic divertor geometry of the HL-2A tokamak with a newly developed module, named trans-neut, within the framework of BOUT++ boundary plasma turbulence code [Z. H. Wang et al., Nucl. Fusion 54, 043019 (2014)]. The physical model includes plasma density, heatmore » and momentum transport equations along with neutral density, and momentum transport equations. Transport dynamics and profile evolutions of both plasma and neutrals are simulated and compared between GP and SMBI in both poloidal and radial directions, which are quite different from one and the other. It finds that the neutrals can penetrate about four centimeters inside the last closed (magnetic) flux surface during SMBI, while they are all deposited outside of the LCF during GP. It is the radial convection and larger inflowing flux which lead to the deeper penetration depth of SMBI and higher fueling efficiency compared to GP.« less

Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

PubMed

Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

2018-05-23

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

From bedside to blackboard: the benefits of teaching molecular biology within a medical context.

PubMed

Sitaraman, Ramakrishnan

2012-01-01

Courses in molecular biology are part of practically every degree program in medicine and the life sciences. Historically, many basic discoveries in this field have resulted from investigations by doctors into the nature of diseases. This essay suggests that medical educators deliberately incorporate such material, whether historical or contemporaneous, into their molecular and cell biology courses. An example of such usage, an early report of the detection of bacteriophage activity on pathogenic bacteria, is discussed in detail. Such an approach can potentially narrow the perceived gap between "basic" and "applied" science. As medicine is so intimately and obviously linked with human welfare, this also provides an avenue for educators to discuss issues of scientific integrity and ethics within a "pure science" course.

Stand-off molecular composition analysis

NASA Astrophysics Data System (ADS)

Hughes, Gary B.; Lubin, Philip; Meinhold, Peter; O'Neill, Hugh; Brashears, Travis; Zhang, Qicheng; Griswold, Janelle; Riley, Jordan; Motta, Caio

2015-09-01

Molecular composition of distant stars is explored by observing absorption spectra. The star produces blackbody radiation that passes through the molecular cloud of vaporized material surrounding the star. Characteristic absorption lines are discernible with a spectrometer, and molecular composition is investigated by comparing spectral observations with known material profiles. Most objects in the solar system—asteroids, comets, planets, moons—are too cold to be interrogated in this manner. Molecular clouds around cold objects consist primarily of volatiles, so bulk composition cannot be probed. Additionally, low volatile density does not produce discernible absorption lines in the faint signal generated by low blackbody temperatures. This paper describes a system for probing the molecular composition of cold solar system targets from a distant vantage. The concept utilizes a directed energy beam to melt and vaporize a spot on a distant target, such as from a spacecraft orbiting the object. With sufficient flux (~10 MW/m2), the spot temperature rises rapidly (to ~2 500 K), and evaporation of all materials on the target surface occurs. The melted spot creates a high-temperature blackbody source, and ejected material creates a molecular plume in front of the spot. Bulk composition is investigated by using a spectrometer to view the heated spot through the ejected material. Spatial composition maps could be created by scanning the surface. Applying the beam to a single spot continuously produces a borehole, and shallow sub-surface composition profiling is also possible. Initial simulations of absorption profiles with laser heating show great promise for molecular composition analysis.

Study the sensitivity of molecular functional groups to bioethanol processing in lipid biopolymer of co-products using DRIFT molecular spectroscopy

NASA Astrophysics Data System (ADS)

Yu, Peiqiang

2011-11-01

To date, there is no study on bioethanol processing-induced changes in molecular structural profiles mainly related to lipid biopolymer. The objectives of this study were to: (1) determine molecular structural changes of lipid related functional groups in the co-products that occurred during bioethanol processing; (2) relatively quantify the antisymmetric CH 3 and CH 2 (ca. 2959 and 2928 cm -1, respectively), symmetric CH 3 and CH 2 (ca. 2871 and 2954 cm -1, respectively) functional groups, carbonyl C dbnd O ester (ca. 1745 cm -1) and unsaturated groups (CH attached to C dbnd C) (ca. 3007 cm -1) spectral intensities as well as their ratios of antisymmetric CH 3 to antisymmetric CH 2, and (3) illustrate the molecular spectral analyses as a research tool to detect for the sensitivity of individual moleculars to the bioethanol processing in a complex plant-based feed and food system without spectral parameterization. The hypothesis of this study was that bioethanol processing changed the molecular structure profiles in the co-products as opposed to original cereal grains. These changes could be detected by infrared molecular spectroscopy and will be related to nutrient utilization. The results showed that bioethanol processing had effects on the functional groups spectral profiles in the co-products. It was found that the CH 3-antisymmetric to CH 2-antisymmetric stretching intensity ratio was changed. The spectral features of carbonyl C dbnd O ester group and unsaturated group were also different. Since the different types of cereal grains (wheat vs. corn) had different sensitivity to the bioethanol processing, the spectral patterns and band component profiles differed between their co-products (wheat DDGS vs. corn DDGS). The multivariate molecular spectral analyses, cluster analysis and principal component analysis of original spectra (without spectral parameterization), distinguished the structural differences between the wheat and wheat DDGS and between the corn and corn DDGS in the antisymmetric and symmetric CH 3 and CH 2 spectral region (ca. 2994-2800 cm -1) and unsaturated group band region (3025-2996 cm -1). Further study is needed to quantify molecular structural changes in relation to nutrient utilization of lipid biopolymer.

Wind Profiles Obtained with a Molecular Direct Detection Doppler Lidar During IHOP-2002

NASA Technical Reports Server (NTRS)

Gentry, Bruce M.; Chen, Huai-Lin; Li, Steven X.; Mathur, Savyasachee; Dobler, Jeremy; Hasselbrack, William; Comer, Joseph

2004-01-01

The Goddard Lidar Observatory for Winds (GLOW) is a mobile direct detection Doppler lidar system which uses the double edge technique to measure the Doppler shift of the molecular backscattered laser signal at a wavelength of 355 nm. In the spring of 2002 GLOW was deployed to the western Oklahoma profiling site (36 deg 33.500 min. N, 100 deg. 36.371 min. W) to participate in the International H2O Project (IHOP). During the IHOP campaign over 240 hours of wind profiles were obtained with the GLOW lidar in support of a variety of scientific investigations.

Teaching microbiology to undergraduate students in the humanities and the social sciences.

PubMed

Oren, Aharon

2015-10-01

This paper summarizes my experiences teaching a 28-hour course on the bacterial world for undergraduate students in the humanities and the social sciences at the Hebrew University of Jerusalem. This course was offered in the framework of a program in which students must obtain credit points for courses offered by other faculties to broaden their education. Most students had little biology in high school and had never been exposed to the basics of chemistry. Using a historical approach, highlighting the work of pioneers such as van Leeuwenhoek, Koch, Fleming, Pasteur, Winogradsky and Woese, I covered a broad area of general, medical, environmental and evolutionary microbiology. The lectures included basic concepts of organic and inorganic chemistry necessary to understand the principles of fermentations and chemoautotrophy, and basic molecular biology to explain biotechnology using transgenic microorganisms and molecular phylogeny. Teaching the basics of microbiology to intelligent students lacking any background in the natural sciences was a rewarding experience. Some students complained that, in spite of my efforts, basic concepts of chemistry remained beyond their understanding. But overall the students' evaluation showed that the course had achieved its goal. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The molecular biology of soft-tissue sarcomas and current trends in therapy.

PubMed

Quesada, Jorge; Amato, Robert

2012-01-01

Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

Profile and Status of Untrained Teachers: Experiences in Basic Schools in Rural Ghana

ERIC Educational Resources Information Center

Tanaka, Chisato

2012-01-01

Untrained teachers are deployed in basic schools in many developing countries as a measure to address enrolment escalation; minimising the financial burden on the government, much of whose education budget is already a recurrent cost. However, there has been little research into untrained teachers. Employing a mixed-methods approach, this article…

A Statewide Profile of Adult Basic Education.

ERIC Educational Resources Information Center

Essex, Martin W.; And Others

A survey of 72 adult basic education (ABE) programs in Ohio was conducted during the 1968-69 school year. Sixty-nine directors handled 447 ABE classes; however, about 40% were handled by three of them. Public school classrooms were the most frequently used facilities (68%). Night classes accounted for 85%. Most of the directors' time was devoted…

Integration of Basic Sciences in Health's Courses

ERIC Educational Resources Information Center

Azzalis, L. A.; Giavarotti, L.; Sato, S. N.; Barros, N. M. T.; Junqueira, V. B. C.; Fonseca, F. L. A.

2012-01-01

Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular Biology are essential to the understanding and treatment of an elevated number of illnesses, but often they are studied separately, with no integration between them. This article proposes a model for basic sciences integration based on problem-based learning (PBL) and…

Senior Computational Scientist | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research in basic and applied molecular biology, immunology, retrovirology, cancer biology, and human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick National Laboratory for Cancer Research (FNLCR). The Cancer & Inflammation Program (CIP),

Secretary | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research programs in basic or applied molecular biology, immunology, retrovirology, cancer biology, or human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick national Laboratory for Cancer Research (FNLCR). The BSP Office provides

Students' Levels of Explanations, Models, and Misconceptions in Basic Quantum Chemistry: A Phenomenographic Study

ERIC Educational Resources Information Center

Stefani, Christina; Tsaparlis, Georgios

2009-01-01

We investigated students' knowledge constructions of basic quantum chemistry concepts, namely atomic orbitals, the Schrodinger equation, molecular orbitals, hybridization, and chemical bonding. Ausubel's theory of meaningful learning provided the theoretical framework and phenomenography the method of analysis. The semi-structured interview with…

Molecular profiles to biology and pathways: a systems biology approach.

PubMed

Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

2016-06-16

Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

Automated tumor analysis for molecular profiling in lung cancer

PubMed Central

Boyd, Clinton; James, Jacqueline A.; Loughrey, Maurice B.; Hougton, Joseph P.; Boyle, David P.; Kelly, Paul; Maxwell, Perry; McCleary, David; Diamond, James; McArt, Darragh G.; Tunstall, Jonathon; Bankhead, Peter; Salto-Tellez, Manuel

2015-01-01

The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics. PMID:26317646

State Education Finance and Governance Profile: Tennessee

ERIC Educational Resources Information Center

Krause, Mike

2010-01-01

This article presents the state education finance and governance profile of Tennessee. The 17th largest state, Tennessee is home to 2.01% of the nation's inhabitants. Funding of K-12 education in Tennessee is accomplished via a formula known as the Basic Educational Program (BEP). This plan primarily utilizes school district enrollment numbers to…

1993/94 Literacy Community Planning Process (LCPP) Profile Analysis.

ERIC Educational Resources Information Center

Ontario Training and Adjustment Board, Toronto.

The Literacy Community Planning Process (LCPP) was intended to assist Ontario communities in comprehensive planning to meet the needs of adult learners requiring training in basic literacy and numeracy. In the first phase, 59 local LCPP committees and 4 literacy networks submitted community profiles to the Literacy Section of the Ontario Training…

The Philip Morris Information Network: A Library Database on an In-House Timesharing System.

ERIC Educational Resources Information Center

DeBardeleben, Marian Z.; And Others

1983-01-01

Outlines a database constructed at Philip Morris Research Center Library which encompasses holdings and circulation and acquisitions records for all items in the library. Host computer (DECSYSTEM-2060), software (BASIC), database design, search methodology, cataloging, and accessibility are noted; sample search, circ-in profile, end user profiles,…

PROSPECT: Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2012-06-01

neoadjuvant therapies on disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular... prognostically distinct subpopulations of patients with resectable NSCLC, and to assess the extent to which these molecular profiles correlate with tumor...overall survival, and will use Cox proportional hazards models and recursive partitioning methods to identify important biomarkers and prognostically

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

DTIC Science & Technology

2014-12-01

smokers [7]. In addition, modulation of global gene expression in the normal epithelium in health smokers is similar in the large and small airways...previously shown that gene-expression profiles in cytologically normal mainstem bronchus epithelium can distinguish smokers with and without lung cancer...spatially mapping the molecular field of injury associated with smoking-related lung cancer. In smokers undergoing resection of lung lesions, high

Genomic profiles of low-grade murine gliomas evolve during progression to glioblastoma. | Office of Cancer Genomics

Cancer.gov

Background: Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear.Methods: We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease.

Influence of macromolecular architecture on necking in polymer extrusion film casting process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pol, Harshawardhan; Banik, Sourya; Azad, Lal Busher

2015-05-22

Extrusion film casting (EFC) is an important polymer processing technique that is used to produce several thousand tons of polymer films/coatings on an industrial scale. In this research, we are interested in understanding quantitatively how macromolecular chain architecture (for example long chain branching (LCB) or molecular weight distribution (MWD or PDI)) influences the necking and thickness distribution of extrusion cast films. We have used different polymer resins of linear and branched molecular architecture to produce extrusion cast films under controlled experimental conditions. The necking profiles of the films were imaged and the velocity profiles during EFC were monitored using particlemore » tracking velocimetry (PTV) technique. Additionally, the temperature profiles were captured using an IR thermography and thickness profiles were calculated. The experimental results are compared with predictions of one-dimensional flow model of Silagy et al{sup 1} wherein the polymer resin rheology is modeled using molecular constitutive equations such as the Rolie-Poly (RP) and extended Pom Pom (XPP). We demonstrate that the 1-D flow model containing the molecular constitutive equations provides new insights into the role of macromolecular chain architecture on film necking.{sup 1}D. Silagy, Y. Demay, and J-F. Agassant, Polym. Eng. Sci., 36, 2614 (1996)« less

Non-Markovian near-infrared Q branch of HCl diluted in liquid Ar.

PubMed

Padilla, Antonio; Pérez, Justo

2013-08-28

By using a non-Markovian spectral theory based in the Kubo cumulant expansion technique, we have qualitatively studied the infrared Q branch observed in the fundamental absorption band of HCl diluted in liquid Ar. The statistical parameters of the anisotropic interaction present in this spectral theory were calculated by means of molecular dynamics techniques, and found that the values of the anisotropic correlation times are significantly greater (by a factor of two) than those previously obtained by fitting procedures or microscopic cell models. This fact is decisive for the observation in the theoretical spectral band of a central Q resonance which is absent in the abundant previous researches carried out with the usual theories based in Kubo cumulant expansion techniques. Although the theory used in this work only allows a qualitative study of the Q branch, we can employ it to study the unknown characteristics of the Q resonance which are difficult to obtain with the quantum simulation techniques recently developed. For example, in this study we have found that the Q branch is basically a non-Markovian (or memory) effect produced by the spectral line interferences, where the PR interferential profile basically determines the Q branch spectral shape. Furthermore, we have found that the Q resonance is principally generated by the first rotational states of the first two vibrational levels, those more affected by the action of the dissolvent.

Strategies for the acquisition of transcriptional and epigenetic information in single cells.

PubMed

Li, Guang; Dzilic, Elda; Flores, Nick; Shieh, Alice; Wu, Sean M

2017-03-01

As the basic unit of living organisms, each single cell has unique molecular signatures and functions. Our ability to uncover the transcriptional and epigenetic signature of single cells has been hampered by the lack of tools to explore this area of research. The advent of microfluidic single cell technology along with single cell genome-wide DNA amplification methods had greatly improved our understanding of the expression variation in single cells. Transcriptional expression profile by multiplex qPCR or genome-wide RNA sequencing has enabled us to examine genes expression in single cells in different tissues. With the new tools, the identification of new cellular heterogeneity, novel marker genes, unique subpopulations, and spatial locations of each single cell can be acquired successfully. Epigenetic modifications for each single cell can also be obtained via similar methods. Based on single cell genome sequencing, single cell epigenetic information including histone modifications, DNA methylation, and chromatin accessibility have been explored and provided valuable insights regarding gene regulation and disease prognosis. In this article, we review the development of strategies to obtain single cell transcriptional and epigenetic data. Furthermore, we discuss ways in which single cell studies may help to provide greater understanding of the mechanisms of basic cardiovascular biology that will eventually lead to improvement in our ability to diagnose disease and develop new therapies.

Biorelevant physicochemical profiling of (E)- and (Z)-resveratrol determined from isomeric mixtures.

PubMed

Orgován, Gábor; Gonda, Imre; Noszál, Béla

2017-05-10

Biorelevant, isomer-specific physicochemical parameters of resveratrol, a multifunctional component in red wines, with cardioprotective, anti-Alzheimer and several other pharmacologic activities were determined. The parameters include site-specific basicities, lipophilicities, solubilities and diffusion constants for the two geometric isomers. The protonation equilibria of (E)- and (Z)-resveratrol were monitored by 1 H NMR-pH titrations. Five closely related auxiliary compounds ((E)-pinostilbene, (Z)-pinostilbene, (E)-pterostilbene, (Z)-pterostilbene and resorcinol) were also studied. Combining the datasets, the group-specific protonation constants of resveratrol isomers were determined. The results show that (Z)-resveratrol is more basic at every protonation site than the (E)-isomer. Lipophilicities are quantified in terms of logP values and were determined by octanol/water partition experiments and quantitative NMR spectroscopy: (E)-resveratrol was found to be more lipophilic. Since the molecular geometries of the isomers differ, diffusion ordered NMR spectroscopy (DOSY) experiments were also carried out to quantify the diffusion capabilities of the isomers: (Z)-resveratrol of bent shape has a slightly higher diffusion coefficient than its extended (E) counterpart. A striking 10-fold difference of water solubility was found in favor of the (Z) isomer, due obviously to the reduced water-repellent character in the more compact molecule. This is so far the greatest recorded solubility difference between geometric isomers of any compounds. Copyright © 2016. Published by Elsevier B.V.

Customized Molecular Phenotyping by Quantitative Gene Expression and Pattern Recognition Analysis

PubMed Central

Akilesh, Shreeram; Shaffer, Daniel J.; Roopenian, Derry

2003-01-01

Description of the molecular phenotypes of pathobiological processes in vivo is a pressing need in genomic biology. We have implemented a high-throughput real-time PCR strategy to establish quantitative expression profiles of a customized set of target genes. It enables rapid, reproducible data acquisition from limited quantities of RNA, permitting serial sampling of mouse blood during disease progression. We developed an easy to use statistical algorithm—Global Pattern Recognition—to readily identify genes whose expression has changed significantly from healthy baseline profiles. This approach provides unique molecular signatures for rheumatoid arthritis, systemic lupus erythematosus, and graft versus host disease, and can also be applied to defining the molecular phenotype of a variety of other normal and pathological processes. PMID:12840047

APPLICATION OF GENOMIC AND PROTEOMIC INDICATORS TO CHARACTERIZE EXPOSURE OF AQUATIC ORGANISMS TO ENVIRONMENTAL CONTAMINANTS

EPA Science Inventory

Advances in molecular biological methods are continually being brought to bear on human health research, from a basic understanding of systems biology to identification of toxicity pathways for environmental stressors and to correlations of molecular indicators with physiological...

75 FR 26970 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

...-496-8551, [email protected] . Name of Committee: Molecular, Cellular and Developmental...: Oncology 1--Basic Translational Integrated Review Group, Cancer Genetics Study Section. Date: June 3-4... 20892, (301) 435-1154, [email protected] . Name of Committee: Molecular, Cellular and Developmental...

Molecular spectroscopy and collisional excitation. [in astrophysics

NASA Technical Reports Server (NTRS)

Green, S.

1975-01-01

The paper examines the basic principles underlying the molecular transitions responsible for interstellar molecular spectra. The energy levels of molecules are discussed in detail with special attention given to the Born-Oppenheimer approximation, the electronic Hamiltonian, and the parameters of vibrational and rotational energy. The probabilities for radiative and collisional transitions are calculated. A brief review of techniques for molecular spectroscopy is presented along with methods used to determine collision cross sections on both an experimental and a theoretical basis.

Molecular aspects of magnetic resonance imaging and spectroscopy.

PubMed

Boesch, C

1999-01-01

Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.

Protein Interactome of Muscle Invasive Bladder Cancer

PubMed Central

Bhat, Akshay; Heinzel, Andreas; Mayer, Bernd; Perco, Paul; Mühlberger, Irmgard; Husi, Holger; Merseburger, Axel S.; Zoidakis, Jerome; Vlahou, Antonia; Schanstra, Joost P.; Mischak, Harald; Jankowski, Vera

2015-01-01

Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder. PMID:25569276

Clinical Metabolomics: The New Metabolic Window for Inborn Errors of Metabolism Investigations in the Post-Genomic Era

PubMed Central

Tebani, Abdellah; Abily-Donval, Lenaig; Afonso, Carlos; Marret, Stéphane; Bekri, Soumeya

2016-01-01

Inborn errors of metabolism (IEM) represent a group of about 500 rare genetic diseases with an overall estimated incidence of 1/2500. The diversity of metabolic pathways involved explains the difficulties in establishing their diagnosis. However, early diagnosis is usually mandatory for successful treatment. Given the considerable clinical overlap between some inborn errors, biochemical and molecular tests are crucial in making a diagnosis. Conventional biological diagnosis procedures are based on a time-consuming series of sequential and segmented biochemical tests. The rise of “omic” technologies offers holistic views of the basic molecules that build a biological system at different levels. Metabolomics is the most recent “omic” technology based on biochemical characterization of metabolites and their changes related to genetic and environmental factors. This review addresses the principles underlying metabolomics technologies that allow them to comprehensively assess an individual biochemical profile and their reported applications for IEM investigations in the precision medicine era. PMID:27447622

MollDE: a homology modeling framework you can click with.

PubMed

Canutescu, Adrian A; Dunbrack, Roland L

2005-06-15

Molecular Integrated Development Environment (MolIDE) is an integrated application designed to provide homology modeling tools and protocols under a uniform, user-friendly graphical interface. Its main purpose is to combine the most frequent modeling steps in a semi-automatic, interactive way, guiding the user from the target protein sequence to the final three-dimensional protein structure. The typical basic homology modeling process is composed of building sequence profiles of the target sequence family, secondary structure prediction, sequence alignment with PDB structures, assisted alignment editing, side-chain prediction and loop building. All of these steps are available through a graphical user interface. MolIDE's user-friendly and streamlined interactive modeling protocol allows the user to focus on the important modeling questions, hiding from the user the raw data generation and conversion steps. MolIDE was designed from the ground up as an open-source, cross-platform, extensible framework. This allows developers to integrate additional third-party programs to MolIDE. http://dunbrack.fccc.edu/molide/molide.php rl_dunbrack@fccc.edu.

Evaluating Kinase ATP Uptake and Tyrosine Phosphorylation using Multiplexed Quantification of Chemically Labeled and Post-Translationally Modified Peptides

PubMed Central

Fang, Bin; Hoffman, Melissa A.; Mirza, Abu-Sayeef; Mishall, Katie M.; Li, Jiannong; Peterman, Scott M.; Smalley, Keiran S. M.; Shain, Kenneth H.; Weinberger, Paul M.; Wu, Jie; Rix, Uwe; Haura, Eric B.; Koomen, John M.

2015-01-01

Cancer biologists and other healthcare researchers face an increasing challenge in addressing the molecular complexity of disease. Biomarker measurement tools and techniques now contribute to both basic science and translational research. In particular, liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) for multiplexed measurements of protein biomarkers has emerged as a versatile tool for systems biology. Assays can be developed for specific peptides that report on protein expression, mutation, or post-translational modification; discovery proteomics data rapidly translated into multiplexed quantitative approaches. Complementary advances in affinity purification enrich classes of enzymes or peptides representing post-translationally modified or chemically labeled substrates. Here, we illustrate the process for the relative quantification of hundreds of peptides in a single LC-MRM experiment. Desthiobiotinylated peptides produced by activity-based protein profiling (ABPP) using ATP probes and tyrosine-phosphorylated peptides are used as examples. These targeted quantification panels can be applied to further understand the biology of human disease. PMID:25782629

Systems Approaches to Biology and Disease Enable Translational Systems Medicine

PubMed Central

Hood, Leroy; Tian, Qiang

2012-01-01

The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate. In the foreseeable future, clinicians, medical researchers, and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information, e.g., whole genome sequences, molecular profiling of diseased tissues, and periodic multi-analyte blood testing of biomarker panels for disease and wellness. The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual. It will also entail proactive participation from all major stakeholders in the health care system. We are at the dawn of predictive, preventive, personalized, and participatory (P4) medicine, the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics, proteomics, nanofluidics, single-cell analysis, and computation strategies in a highly-orchestrated discipline we termed translational systems medicine. PMID:23084773

Neurogliaform cortical interneurons derive from cells in the preoptic area

PubMed Central

Cadilhac, Christelle; Prados, Julien; Holtmaat, Anthony

2018-01-01

Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental specification. Here we identified the developmental trajectory of neurogliaform cells (NGCs), the main effectors of a powerful inhibitory motif recruited by long-range connections. Using in vivo genetic lineage-tracing in mice, we report that NGCs originate from a specific pool of 5-HT3AR-expressing Hmx3+ cells located in the preoptic area (POA). Hmx3-derived 5-HT3AR+ cortical interneurons (INs) expressed the transcription factors PROX1, NR2F2, the marker reelin but not VIP and exhibited the molecular, morphological and electrophysiological profile of NGCs. Overall, these results indicate that NGCs are a distinct class of INs with a unique developmental trajectory and open the possibility to study their specific functional contribution to cortical inhibitory microcircuit motifs. PMID:29557780

Magnesium supplementation, metabolic and inflammatory markers, and global genomic and proteomic profiling: a randomized, double-blind, controlled, crossover trial in overweight individuals.

PubMed

Chacko, Sara A; Sul, James; Song, Yiqing; Li, Xinmin; LeBlanc, James; You, Yuko; Butch, Anthony; Liu, Simin

2011-02-01

Dietary magnesium intake has been favorably associated with reduced risk of metabolic outcomes in observational studies; however, few randomized trials have introduced a systems-biology approach to explore molecular mechanisms of pleiotropic metabolic actions of magnesium supplementation. We examined the effects of oral magnesium supplementation on metabolic biomarkers and global genomic and proteomic profiling in overweight individuals. We undertook this randomized, crossover, pilot trial in 14 healthy, overweight volunteers [body mass index (in kg/m(2)) ≥25] who were randomly assigned to receive magnesium citrate (500 mg elemental Mg/d) or a placebo for 4 wk with a 1-mo washout period. Fasting blood and urine specimens were collected according to standardized protocols. Biochemical assays were conducted on blood specimens. RNA was extracted and subsequently hybridized with the Human Gene ST 1.0 array (Affymetrix, Santa Clara, CA). Urine proteomic profiling was analyzed with the CM10 ProteinChip array (Bio-Rad Laboratories, Hercules, CA). We observed that magnesium treatment significantly decreased fasting C-peptide concentrations (change: -0.4 ng/mL after magnesium treatment compared with +0.05 ng/mL after placebo treatment; P = 0.004) and appeared to decrease fasting insulin concentrations (change: -2.2 μU/mL after magnesium treatment compared with 0.0 μU/mL after placebo treatment; P = 0.25). No consistent patterns were observed across inflammatory biomarkers. Gene expression profiling revealed up-regulation of 24 genes and down-regulation of 36 genes including genes related to metabolic and inflammatory pathways such as C1q and tumor necrosis factor-related protein 9 (C1QTNF9) and pro-platelet basic protein (PPBP). Urine proteomic profiling showed significant differences in the expression amounts of several peptides and proteins after treatment. Magnesium supplementation for 4 wk in overweight individuals led to distinct changes in gene expression and proteomic profiling consistent with favorable effects on several metabolic pathways. This trial was registered at clinicaltrials.gov as NCT00737815.

Molecular modelling of protein-protein/protein-solvent interactions

NASA Astrophysics Data System (ADS)

Luchko, Tyler

The inner workings of individual cells are based on intricate networks of protein-protein interactions. However, each of these individual protein interactions requires a complex physical interaction between proteins and their aqueous environment at the atomic scale. In this thesis, molecular dynamics simulations are used in three theoretical studies to gain insight at the atomic scale about protein hydration, protein structure and tubulin-tubulin (protein-protein) interactions, as found in microtubules. Also presented, in a fourth project, is a molecular model of solvation coupled with the Amber molecular modelling package, to facilitate further studies without the need of explicitly modelled water. Basic properties of a minimally solvated protein were calculated through an extended study of myoglobin hydration with explicit solvent, directly investigating water and protein polarization. Results indicate a close correlation between polarization of both water and protein and the onset of protein function. The methodology of explicit solvent molecular dynamics was further used to study tubulin and microtubules. Extensive conformational sampling of the carboxy-terminal tails of 8-tubulin was performed via replica exchange molecular dynamics, allowing the characterisation of the flexibility, secondary structure and binding domains of the C-terminal tails through statistical analysis methods. Mechanical properties of tubulin and microtubules were calculated with adaptive biasing force molecular dynamics. The function of the M-loop in microtubule stability was demonstrated in these simulations. The flexibility of this loop allowed constant contacts between the protofilaments to be maintained during simulations while the smooth deformation provided a spring-like restoring force. Additionally, calculating the free energy profile between the straight and bent tubulin configurations was used to test the proposed conformational change in tubulin, thought to cause microtubule destabilization. No conformational change was observed but a nucleotide dependent 'softening' of the interaction was found instead, suggesting that an entropic force in a microtubule configuration could be the mechanism of microtubule collapse. Finally, to overcome much of the computational costs associated with explicit soIvent calculations, a new combination of molecular dynamics with the 3D-reference interaction site model (3D-RISM) of solvation was integrated into the Amber molecular dynamics package. Our implementation of 3D-RISM shows excellent agreement with explicit solvent free energy calculations. Several optimisation techniques, including a new multiple time step method, provide a nearly 100 fold performance increase, giving similar computational performance to explicit solvent.

Rocket Science 101 Interactive Educational Program

NASA Technical Reports Server (NTRS)

Armstrong, Dennis; Funkhouse, Deborah; DiMarzio, Donald

2007-01-01

To better educate the public on the basic design of NASA s current mission rockets, Rocket Science 101 software has been developed as an interactive program designed to retain a user s attention and to teach about basic rocket parts. This program also has helped to expand NASA's presence on the Web regarding educating the public about the Agency s goals and accomplishments. The software was designed using Macromedia s Flash 8. It allows the user to select which type of rocket they want to learn about, interact with the basic parts, assemble the parts to create the whole rocket, and then review the basic flight profile of the rocket they have built.

Interfacial layering and capillary roughness in immiscible liquids.

PubMed

Geysermans, P; Pontikis, V

2010-08-21

The capillary roughness and the atomic density profiles of extended interfaces between immiscible liquids are determined as a function of the interface area by using molecular dynamics and Lennard-Jones (12-6) potentials. We found that with increasing area, the interface roughness diverges logarithmically, thus fitting the theoretical mean-field prediction. In systems small enough for the interfacial roughness not to blur the structural details, atomic density profiles across the fluid interface are layered with correlation length in the range of molecular correlations in liquids. On increasing the system size, the amplitude of the thermally excited position fluctuations of the interface increases, thus causing layering to rapidly vanish, if density profiles are computed without special care. In this work, we present and validate a simple method, operating in the direct space, for extracting from molecular dynamics trajectories the "intrinsic" structure of a fluid interface that is the local density profile of the interface cleaned from capillary wave effects. Estimated values of interfacial properties such as the tension, the intrinsic width, and the lower wavelength limit of position fluctuations are in agreement with results collected from the literature.

Profiling of the molecular weight and structural isomer abundance of macroalgae-derived phlorotannins.

PubMed

Heffernan, Natalie; Brunton, Nigel P; FitzGerald, Richard J; Smyth, Thomas J

2015-01-16

Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene) unique to macroalgae. These phenolic compounds are integral structural components of the cell wall in brown algae, but also play many secondary ecological roles such as protection from UV radiation and defense against grazing. This study employed Ultra Performance Liquid Chromatography (UPLC) with tandem mass spectrometry to investigate isomeric complexity and observed differences in phlorotannins derived from macroalgae harvested off the Irish coast (Fucus serratus, Fucus vesiculosus, Himanthalia elongata and Cystoseira nodicaulis). Antioxidant activity and total phenolic content assays were used as an index for producing phlorotannin fractions, enriched using molecular weight cut-off dialysis with subsequent flash chromatography to profile phlorotannin isomers in these macroalgae. These fractions were profiled using UPLC-MS with multiple reaction monitoring (MRM) and the level of isomerization for specific molecular weight phlorotannins between 3 and 16 monomers were determined. The majority of the low molecular weight (LMW) phlorotannins were found to have a molecular weight range equivalent to 4-12 monomers of phloroglucinol. The level of isomerization within the individual macroalgal species differed, resulting in substantially different numbers of phlorotannin isomers for particular molecular weights. F. vesiculosus had the highest number of isomers of 61 at one specific molecular mass, corresponding to 12 phloroglucinol units (PGUs). These results highlight the complex nature of these extracts and emphasize the challenges involved in structural elucidation of these compounds.

Profiling of the Molecular Weight and Structural Isomer Abundance of Macroalgae-Derived Phlorotannins

PubMed Central

Heffernan, Natalie; Brunton, Nigel P.; FitzGerald, Richard J.; Smyth, Thomas J.

2015-01-01

Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene) unique to macroalgae. These phenolic compounds are integral structural components of the cell wall in brown algae, but also play many secondary ecological roles such as protection from UV radiation and defense against grazing. This study employed Ultra Performance Liquid Chromatography (UPLC) with tandem mass spectrometry to investigate isomeric complexity and observed differences in phlorotannins derived from macroalgae harvested off the Irish coast (Fucus serratus, Fucus vesiculosus, Himanthalia elongata and Cystoseira nodicaulis). Antioxidant activity and total phenolic content assays were used as an index for producing phlorotannin fractions, enriched using molecular weight cut-off dialysis with subsequent flash chromatography to profile phlorotannin isomers in these macroalgae. These fractions were profiled using UPLC-MS with multiple reaction monitoring (MRM) and the level of isomerization for specific molecular weight phlorotannins between 3 and 16 monomers were determined. The majority of the low molecular weight (LMW) phlorotannins were found to have a molecular weight range equivalent to 4–12 monomers of phloroglucinol. The level of isomerization within the individual macroalgal species differed, resulting in substantially different numbers of phlorotannin isomers for particular molecular weights. F. vesiculosus had the highest number of isomers of 61 at one specific molecular mass, corresponding to 12 phloroglucinol units (PGUs). These results highlight the complex nature of these extracts and emphasize the challenges involved in structural elucidation of these compounds. PMID:25603345

A Comprehensive Tool and Analytical Pathway for Differential Molecular Profiling and Biomarker Discovery

DTIC Science & Technology

2014-10-20

three possiblities: AKR , B6, and BALB_B) and MUP Protein (containing two possibilities: Intact and Denatured), then you can view a plot of the Strain...the tags for the last two labels. Again, if the attribute Strain has three tags: AKR , B6, 74 Distribution A . Approved for public release...AFRL-RH-WP-TR-2014-0131 A COMPREHENSIVE TOOL AND ANALYTICAL PATHWAY FOR DIFFERENTIAL MOLECULAR PROFILING AND BIOMARKER DISCOVERY

The Human Cell Atlas.

PubMed

Regev, Aviv; Teichmann, Sarah A; Lander, Eric S; Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

2017-12-05

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

The kinematics of the molecular gas in Centaurus A

NASA Technical Reports Server (NTRS)

Quillen, A. C.; De Zeeuw, P. T.; Phinney, E. S.; Phillips, T. G.

1992-01-01

The CO (2-1) emission along the inner dust lane of Centaurus A, observed with the Caltech Submillimeter Observatory on Mauna Kea, shows the molecular gas to be in a thin disk, with a velocity dispersion of only about 10 km/s. The observed line profiles are broadened considerably due to beam smearing of the gas velocity field. The profile shapes are inconsistent with planar circular and noncircular motion. However, a warped disk in a prolate potential provides a good fit to the profile shapes. The morphology and kinematics of the molecular gas is similar to that of the ionized material, seen in H-alpha. The best-fitting warped disk model not only matches the optical appearance of the dust lane but also agrees with the large-scale map of the CO emission and is consistent with H I measurements at larger radii.

The Cancer Genome Atlas Pan-Cancer Analysis Project

PubMed Central

Weinstein, John N.; Collisson, Eric A.; Mills, Gordon B.; Shaw, Kenna M.; Ozenberger, Brad A.; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M.

2014-01-01

Cancer can take hundreds of different forms depending on the location, cell of origin and spectrum of genomic alterations that promote oncogenesis and affect therapeutic response. Although many genomic events with direct phenotypic impact have been identified, much of the complex molecular landscape remains incompletely charted for most cancer lineages. For that reason, The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumours to discover molecular aberrations at the DNA, RNA, protein, and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences, and emergent themes across tumour lineages. The Pan-Cancer initiative compares the first twelve tumour types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumour types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849

The Human Cell Atlas

PubMed Central

Amit, Ido; Benoist, Christophe; Birney, Ewan; Bodenmiller, Bernd; Campbell, Peter; Carninci, Piero; Clatworthy, Menna; Clevers, Hans; Deplancke, Bart; Dunham, Ian; Eberwine, James; Eils, Roland; Enard, Wolfgang; Farmer, Andrew; Fugger, Lars; Göttgens, Berthold; Hacohen, Nir; Haniffa, Muzlifah; Hemberg, Martin; Kim, Seung; Klenerman, Paul; Kriegstein, Arnold; Lein, Ed; Linnarsson, Sten; Lundberg, Emma; Lundeberg, Joakim; Majumder, Partha; Marioni, John C; Merad, Miriam; Mhlanga, Musa; Nawijn, Martijn; Netea, Mihai; Nolan, Garry; Pe'er, Dana; Phillipakis, Anthony; Ponting, Chris P; Quake, Stephen; Reik, Wolf; Rozenblatt-Rosen, Orit; Sanes, Joshua; Satija, Rahul; Schumacher, Ton N; Shalek, Alex; Shapiro, Ehud; Sharma, Padmanee; Shin, Jay W; Stegle, Oliver; Stratton, Michael; Stubbington, Michael J T; Theis, Fabian J; Uhlen, Matthias; van Oudenaarden, Alexander; Wagner, Allon; Watt, Fiona; Weissman, Jonathan; Wold, Barbara; Xavier, Ramnik; Yosef, Nir

2017-01-01

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community. PMID:29206104

The first decade of MALDI protein profiling: a lesson in translational biomarker research.

PubMed

Albrethsen, Jakob

2011-05-16

MALDI protein profiling has identified several important challenges in omics-based biomarker research. First, research into the analytical performance of a novel omics-platform of potential diagnostic impact must be carried out in a critical manner and according to common guidelines. Evaluation studies should be performed at an early time and preferably before massive advancement into explorative biomarker research. In particular, MALDI profiling underscores the need for an adequate understanding of the causal relationship between molecular abundance and the quantitative measure in multivariate biomarker research. Secondly, MALDI profiling has raised awareness of the significant risk of false-discovery in biomarker research due to several confounding factors, including sample processing and unspecific host-response to disease. Here, the experience from MALDI profiling supports that a central challenge in unbiased molecular profiling is to pinpoint the aberrations of clinical interest among potentially massive unspecific changes that can accompany disease. The lessons from the first decade of MALDI protein profiling are relevant for future efforts in advancing omics-based biomarker research beyond the laboratory setting and into clinical verification. Copyright © 2011 Elsevier B.V. All rights reserved.

Technetium-99m: basic nuclear physics and chemical properties.

PubMed

Castronovo, F P

1975-05-01

The nuclear physics and chemical properties of technetium-99m are reviewed. The review of basic nuclear physics includes: classification of nuclides, nuclear stability, production of radionuclides, artificial production of molybdenum-99, production of technetium 99m and -99Mo-99mTc generators. The discussion of the chemistry of technetium includes a profile of several -99mCc-labeled radiopharmaceuticals.

I-N-D-E-P-E-N-D-E-N-T: Increasing Reading Independence for Students with Dyslexia

ERIC Educational Resources Information Center

Milner, Diane Hansen

2017-01-01

Due to their unique brain profile, children with dyslexia struggle with acquiring basic literacy skills. Even after basic reading skills have been learned students with dyslexia may still struggle greatly with generalizing their skills to new contexts. Researchers have found that 75 percent of children identified with reading problems in third…

GEOMETRY-INDEPENDENT DETERMINATION OF RADIAL DENSITY DISTRIBUTIONS IN MOLECULAR CLOUD CORES AND OTHER ASTRONOMICAL OBJECTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krčo, Marko; Goldsmith, Paul F., E-mail: marko@astro.cornell.edu

2016-05-01

We present a geometry-independent method for determining the shapes of radial volume density profiles of astronomical objects whose geometries are unknown, based on a single column density map. Such profiles are often critical to understand the physics and chemistry of molecular cloud cores, in which star formation takes place. The method presented here does not assume any geometry for the object being studied, thus removing a significant source of bias. Instead, it exploits contour self-similarity in column density maps, which appears to be common in data for astronomical objects. Our method may be applied to many types of astronomical objectsmore » and observable quantities so long as they satisfy a limited set of conditions, which we describe in detail. We derive the method analytically, test it numerically, and illustrate its utility using 2MASS-derived dust extinction in molecular cloud cores. While not having made an extensive comparison of different density profiles, we find that the overall radial density distribution within molecular cloud cores is adequately described by an attenuated power law.« less

Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

PubMed Central

Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

2014-01-01

The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

Quantitative image analysis of cellular heterogeneity in breast tumors complements genomic profiling.

PubMed

Yuan, Yinyin; Failmezger, Henrik; Rueda, Oscar M; Ali, H Raza; Gräf, Stefan; Chin, Suet-Feung; Schwarz, Roland F; Curtis, Christina; Dunning, Mark J; Bardwell, Helen; Johnson, Nicola; Doyle, Sarah; Turashvili, Gulisa; Provenzano, Elena; Aparicio, Sam; Caldas, Carlos; Markowetz, Florian

2012-10-24

Solid tumors are heterogeneous tissues composed of a mixture of cancer and normal cells, which complicates the interpretation of their molecular profiles. Furthermore, tissue architecture is generally not reflected in molecular assays, rendering this rich information underused. To address these challenges, we developed a computational approach based on standard hematoxylin and eosin-stained tissue sections and demonstrated its power in a discovery and validation cohort of 323 and 241 breast tumors, respectively. To deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm based on tumor cellularity to increase the comparability of copy number profiles between samples. We next devised a predictor for survival in estrogen receptor-negative breast cancer that integrated both image-based and gene expression analyses and significantly outperformed classifiers that use single data types, such as microarray expression signatures. Image processing also allowed us to describe and validate an independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative, image-based method could benefit any large-scale cancer study by refining and complementing molecular assays of tumor samples.

Microendophenotypes of psychiatric disorders: phenotypes of psychiatric disorders at the level of molecular dynamics, synapses, neurons, and neural circuits.

PubMed

Kida, S; Kato, T

2015-01-01

Psychiatric disorders are caused not only by genetic factors but also by complicated factors such as environmental ones. Moreover, environmental factors are rarely quantitated as biological and biochemical indicators, making it extremely difficult to understand the pathological conditions of psychiatric disorders as well as their underlying pathogenic mechanisms. Additionally, we have actually no other option but to perform biological studies on postmortem human brains that display features of psychiatric disorders, thereby resulting in a lack of experimental materials to characterize the basic biology of these disorders. From these backgrounds, animal, tissue, or cell models that can be used in basic research are indispensable to understand biologically the pathogenic mechanisms of psychiatric disorders. In this review, we discuss the importance of microendophenotypes of psychiatric disorders, i.e., phenotypes at the level of molecular dynamics, neurons, synapses, and neural circuits, as targets of basic research on these disorders.

Molecular cloning and transcriptional analysis of a NPY receptor-like in common Chinese cuttlefish Sepiella japonica

NASA Astrophysics Data System (ADS)

Yang, Jingwen; Xu, Yuchao; Xu, Ke; Ping, Hongling; Shi, Huilai; Lü, Zhenming; Wu, Changwen; Wang, Tianming

2017-08-01

Neuropeptide Y (NPY) has a pivotal role in the regulation of many physiological processes. In this study, the gene encoding a NPY receptor-like from the common Chinese cuttlefish Sepiella japonica (SjNPYR-like) was identified and characterized. The full-length SjNPYR-like cDNA was cloned containing a 492-bp of 5' untranslated region (UTR), 1 182 bp open reading frame (ORF) encoding a protein of 393 amino acid residues, and 228 bp of 3' UTR. The putative protein was predicted to have a molecular weight of 45.54 kDa and an isoelectric point (pI) of 8.13. By informatic analyses, SjNPYR-like was identified as belonging to the class A G protein coupled receptor (GPCR) family (the rhodopsin-type). The amino acid sequence contained 12 potential phosphorylation sites and five predicted N-linked glycosylation sites. Multiple sequence alignment and 3D structure modeling were conducted to clarify SjNPYR bioinformatics characteristics. Phylogenetic analysis identifies it as an NPYR with identity of 33% to Lymnaea stagnalis NPFR. Transmembrane properties of SjNPYR-like were demonstrated in vitro using HEK293 cells and the pEGFP-N1 plasmid. Relative quantification of SjNPYR-like mRNA level confirmed a high level expression and broad distribution of SjNPYR - like in various tissues of female S. japonica. In addition, the transcriptional profile of SjNPYR - like in the brain, liver, and ovary during gonadal development was analyzed. The results provide basic understanding on the molecular characteristics of SjNPYR-like and its potentially physical functions.

Gene integrated set profile analysis: a context-based approach for inferring biological endpoints

PubMed Central

Kowalski, Jeanne; Dwivedi, Bhakti; Newman, Scott; Switchenko, Jeffery M.; Pauly, Rini; Gutman, David A.; Arora, Jyoti; Gandhi, Khanjan; Ainslie, Kylie; Doho, Gregory; Qin, Zhaohui; Moreno, Carlos S.; Rossi, Michael R.; Vertino, Paula M.; Lonial, Sagar; Bernal-Mizrachi, Leon; Boise, Lawrence H.

2016-01-01

The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an ‘integrate by intersection’ (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance. PMID:26826710

78 FR 60296 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

... 20892, 301-435-1501, [email protected] . Name of Committee: Genes, Genomes, and Genetics Integrated Review Group; Prokaryotic Cell and Molecular Biology Study Section. Date: October 25, 2013. Time: 8:00 a... Committee: Oncology 1-Basic Translational Integrated Review Group; Cancer Molecular Pathobiology Study...

The Molecular Basis of Development.

ERIC Educational Resources Information Center

Gehring, Walter J.

1985-01-01

Basic architecture of embryo development appears to be under homeobox control (a short stretch of DNA). Outlines research on this genetic segment in fruit flies which led to identification of this control on the embryo's spatial organization. Indicates that molecular mechanisms underlying development may be much more universal than previously…

INCONSISTENCIES BETWEEN CYTOKINE PROFILES, ANTIBODY RESPONSES, AND RESPIRATORY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO ISOCYANATES

EPA Science Inventory

Cytokine profiling of local lymph node responses has been proposed as a simple test to identify chemicals, such as low molecular weight diisocyanates, that pose a significant risk of occupational asthma. Previously, we reported cytokine mRNA profiles for dinitrochlorobenzene (DNC...

Physical Fitness Profile in Adults with Intellectual Disabilities: Differences between Levels of Sport Practice

ERIC Educational Resources Information Center

Cuesta-Vargas, Antonio Ignacio; Paz-Lourido, Berta; Rodriguez, Alejandro

2011-01-01

Neuromuscular and aerobic capacity can be reduced in people with intellectual disabilities (ID). Previous studies suggest these individuals might be particularly susceptible to losing basic functions because of poor physical fitness. The aim of this study is to describe the physical fitness profile of adult athletes with ID and identify whether…

A. C. C. Fact Book: A Statistical Profile of Allegany Community College and the Community It Serves.

ERIC Educational Resources Information Center

Andersen, Roger C.

This document is intended to be an authoritative compilation of frequently referenced basic facts concerning Allegany Community College (ACC) in Maryland. It is a statistical profile of ACC and the community it serves, divided into six sections: enrollment, students, faculty, community, support services, and general college related information.…

Assessing Students' Use of LinkedIn in a Business and Professional Communication Course

ERIC Educational Resources Information Center

Slone, Amanda Ruth; Gaffney, Amy L. H.

2016-01-01

This paper examined the practice of using LinkedIn as a tool for teaching students how to create a professional online presence. A descriptive analysis of student LinkedIn profiles revealed that students included some basic requirements, but many students still neglected to fully complete the profile, thereby leaving out some important information…

Design and evaluation of basic standard encryption algorithm modules using nanosized complementary metal oxide semiconductor molecular circuits

NASA Astrophysics Data System (ADS)

Masoumi, Massoud; Raissi, Farshid; Ahmadian, Mahmoud; Keshavarzi, Parviz

2006-01-01

We are proposing that the recently proposed semiconductor-nanowire-molecular architecture (CMOL) is an optimum platform to realize encryption algorithms. The basic modules for the advanced encryption standard algorithm (Rijndael) have been designed using CMOL architecture. The performance of this design has been evaluated with respect to chip area and speed. It is observed that CMOL provides considerable improvement over implementation with regular CMOS architecture even with a 20% defect rate. Pseudo-optimum gate placement and routing are provided for Rijndael building blocks and the possibility of designing high speed, attack tolerant and long key encryptions are discussed.

Surface roughness formation during shot peen forming

NASA Astrophysics Data System (ADS)

Koltsov, V. P.; Vinh, Le Tri; Starodubtseva, D. A.

2018-03-01

Shot peen forming (SPF) is used for forming panels and skins, and for hardening. As a rule, shot peen forming is performed after milling. Surface roughness is a complex structure, a combination of an original microrelief and shot peen forming indentations of different depths and chaotic distribution along the surface. As far as shot peen forming is a random process, surface roughness resulted from milling and shot peen forming is random too. During roughness monitoring, it is difficult to determine the basic surface area which would ensure accurate results. It can be assumed that the basic area depends on the random roughness which is characterized by the degree of shot peen forming coverage. The analysis of depth and shot peen forming indentations distribution along the surface made it possible to identify the shift of an original center profile plane and create a mathematical model for the arithmetic mean deviation of the profile. Experimental testing proved model validity and determined an inversely proportional dependency of the basic area on the degree of coverage.

Well-posed two-temperature constitutive equations for stable dense fluid shock waves using molecular dynamics and generalizations of Navier-Stokes-Fourier continuum mechanics.

PubMed

Hoover, Wm G; Hoover, Carol G

2010-04-01

Guided by molecular dynamics simulations, we generalize the Navier-Stokes-Fourier constitutive equations and the continuum motion equations to include both transverse and longitudinal temperatures. To do so we partition the contributions of the heat transfer, the work done, and the heat flux vector between the longitudinal and transverse temperatures. With shockwave boundary conditions time-dependent solutions of these equations converge to give stationary shockwave profiles. The profiles include anisotropic temperature and can be fitted to molecular dynamics results, demonstrating the utility and simplicity of a two-temperature description of far-from-equilibrium states.

The role of molecular diagnostic testing in the management of thyroid nodules.

PubMed

Moore, Maureen D; Panjwani, Suraj; Gray, Katherine D; Finnerty, Brendan M; Zarnegar, Rasa; Fahey, Thomas J

2017-06-01

Fine needle aspiration (FNA) with cytologic examination remains the standard of care for investigation of thyroid nodules. However, as many as 30% of FNA samples are cytologically indeterminate for malignancy, which confounds clinical management. To reduce the burden of repeat diagnostic testing and unnecessary surgery, there has been extensive investigation into molecular markers that can be detected on FNA specimens to more accurately stratify a patient's risk of malignancy. Areas covered: In this review, the authors discuss recent evidence and progress in molecular markers used in the diagnosis of thyroid cancer highlighting somatic gene alterations, molecular technologies and microRNA analysis. Expert commentary: The goal of molecular markers is to improve diagnostic accuracy and aid clinicians in the preoperative management of thyroid lesions. Modalities such as direct mutation analysis, mRNA gene expression profiling, next-generation sequencing, and miRNA expression profiling have been explored to improve the diagnostic accuracy of thyroid nodule FNA. Although no perfect test has been discovered, molecular diagnostic testing has revolutionized the management of thyroid nodules.

Molecular analysis of Aspergillus section Flavi isolated from Brazil nuts.

PubMed

Gonçalves, Juliana Soares; Ferracin, Lara Munique; Carneiro Vieira, Maria Lucia; Iamanaka, Beatriz Thie; Taniwaki, Marta Hiromi; Pelegrinelli Fungaro, Maria Helena

2012-04-01

Brazil nuts are an important export market in its main producing countries, including Brazil, Bolivia, and Peru. Approximately 30,000 tons of Brazil nuts are harvested each year. However, substantial nut contamination by Aspergillus section Flavi occurs with subsequent production of aflatoxins. In our study, Aspergillus section Flavi were isolated from Brazil nuts (Bertholletia excelsa), and identified by morphological and molecular means. We obtained 241 isolates from nut samples, 41% positive for aflatoxin production. Eighty-one isolates were selected for molecular investigation. Pairwise genetic distances among isolates and phylogenetic relationships were assessed. The following Aspergillus species were identified: A. flavus, A. caelatus, A. nomius, A. tamarii, A. bombycis, and A. arachidicola. Additionally, molecular profiles indicated a high level of nucleotide variation within β-tubulin and calmodulin gene sequences associated with high genetic divergence from RAPD data. Among the 81 isolates analyzed by molecular means, three of them were phylogenetically distinct from all other isolates representing the six species of section Flavi. A putative novel species was identified based on molecular profiles.

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

PubMed Central

Krienen, Fenna M.; Yeo, B. T. Thomas; Ge, Tian; Buckner, Randy L.; Sherwood, Chet C.

2016-01-01

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute’s human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections. PMID:26739559

Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.

PubMed

Ortiz, Michael V; Kobos, Rachel; Walsh, Michael; Slotkin, Emily K; Roberts, Stephen; Berger, Michael F; Hameed, Meera; Solit, David; Ladanyi, Marc; Shukla, Neerav; Kentsis, Alex

2016-08-01

Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations. This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence-Based Medicine. There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1-2), eight (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4). The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. The development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials. © 2016 Wiley Periodicals, Inc.

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain.

PubMed

Krienen, Fenna M; Yeo, B T Thomas; Ge, Tian; Buckner, Randy L; Sherwood, Chet C

2016-01-26

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.

New clinical trial opens to provide evaluation, tumor profiling and follow-up of patients with gastric tumors | Center for Cancer Research

Cancer.gov

This new clinical trial will collect samples of gastric tumor tissue from patients with the goal to use the molecular profiles to design treatments that work better by targeting a specific cancer tumor profile.  Learn more...

Using Restriction Mapping to Teach Basic Skills in the Molecular Biology Lab

ERIC Educational Resources Information Center

Walsh, Lauren; Shaker, Elizabeth; De Stasio, Elizabeth A.

2007-01-01

Digestion of DNA with restriction enzymes, calculation of volumes and concentrations of reagents for reactions, and the separation of DNA fragments by agarose gel electrophoresis are common molecular biology techniques that are best taught through repetition. The following open-ended, investigative laboratory exercise in plasmid restriction…

Molecular Recognition: Detection of Colorless Compounds Based on Color Change

ERIC Educational Resources Information Center

Khalafi, Lida; Kashani, Samira; Karimi, Javad

2016-01-01

A laboratory experiment is described in which students measure the amount of cetirizine in allergy-treatment tablets based on molecular recognition. The basis of recognition is competition of cetirizine with phenolphthalein to form an inclusion complex with ß-cyclodextrin. Phenolphthalein is pinkish under basic condition, whereas it's complex form…

The Use of Molecular Modeling Programs in Medicinal Chemistry Instruction.

ERIC Educational Resources Information Center

Harrold, Marc W.

1992-01-01

This paper describes and evaluates the use of a molecular modeling computer program (Alchemy II) in a pharmaceutical education program. Provided are the hardware requirements and basic program features as well as several examples of how this program and its features have been applied in the classroom. (GLR)

The impact of culture collections on molecular identification, taxonomy, and solving real problems

USDA-ARS?s Scientific Manuscript database

Among the fungi, Fusarium has stood out as a major focus for culture collection resource development over the last century. This has facilitated unprecedented molecular taxonomic advancements, which in turn has led to problem solving in plant pathology, mycotoxicology, medical mycology, and basic re...

Nitric oxide assisted C60 secondary ion mass spectrometry for molecular depth profiling of polyelectrolyte multilayers.

PubMed

Zappalà, G; Motta, V; Tuccitto, N; Vitale, S; Torrisi, A; Licciardello, A

2015-12-15

Secondary ion mass spectrometry (SIMS) with polyatomic primary ions provides a successful tool for molecular depth profiling of polymer systems, relevant in many technological applications. Widespread C60 sources, however, cause in some polymers extensive damage with loss of molecular information along depth. We study a method, based on the use of a radical scavenger, for inhibiting ion-beam-induced reactions causing sample damage. Layered polystyrene sulfonate and polyacrylic acid based polyelectrolyte films, behaving differently towards C60 beam-induced damage, were selected and prepared as model systems. They were depth profiled by means of time-of-flight (TOF)-SIMS in dual beam mode, using fullerene ions for sputtering. Nitric oxide was introduced into the analysis chamber as a radical scavenger. The effect of sample cooling combined with NO-dosing on the quality of depth profiles was explored. NO-dosing during C60-SIMS depth profiling of >1 micrometer-thick multilayered polyelectrolytes allows detection, along depth, of characteristic fragments from systems otherwise damaged by C60 bombardment, and increases sputtering yield by more than one order of magnitude. By contrast, NO has little influence on those layers that are well profiled with C60 alone. Such leveling effect, more pronounced at low temperature, leads to a dramatic improvement of profile quality, with a clear definition of interfaces. NO-dosing provides a tool for extending the applicability, in SIMS depth profiling, of the widely spread fullerene ion sources. In view of the acceptable erosion rates on inorganics, obtainable with C60, the method could be of relevance also in connection with the 3D-imaging of hybrid polymer/inorganic systems. Copyright © 2015 John Wiley & Sons, Ltd.

Major Upgrades to the AIRS Version-6 Water Vapor Profile Methodology

NASA Technical Reports Server (NTRS)

Susskind, Joel; Blaisdell, John; Iredell, Lena

2015-01-01

This research is a continuation of part of what was shown at the last AIRS Science Team Meeting and the AIRS 2015 NetMeeting. AIRS Version 6 was finalized in late 2012 and is now operational. Version 6 contained many significant improvements in retrieval methodology compared to Version 5. Version 6 retrieval methodology used for the water vapor profile q(p) and ozone profile O3(p) retrievals is basically unchanged from Version 5, or even from Version 4. Subsequent research has made significant improvements in both water vapor and O3 profiles compared to Version 6.

The clinical impact of using complex molecular profiling strategies in routine oncology practice.

PubMed

Laes, Jean-François; Aftimos, Philippe; Barthelemy, Philippe; Bellmunt, Joaquim; Berchem, Guy; Camps, Carlos; Peñas, Ramón de Las; Finzel, Ana; García-Foncillas, Jesús; Hervonen, Petteri; Wahid, Ibrahim; Joensuu, Timo; Kathan, Louis; Kong, Anthony; Mackay, James; Mikropoulos, Christos; Mokbel, Kefah; Mouysset, Jean-Loup; Odarchenko, Sergey; Perren, Timothy J; Pienaar, Rika; Regonesi, Carlos; Alkhayyat, Shadi Salem; El Kinge, Abdul Rahman; Abulkhair, Omalkhair; Galal, Khaled Morsi; Ghanem, Hady; El Karak, Fadi; Garcia, Angel; Ghitti, Gregori; Sadik, Helen

2018-04-17

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.

Molecular cloning and expression profile of an ATP-binding cassette (ABC) transporter gene from the hemipteran insect Nilaparvata lugens.

PubMed

Zha, W J; Li, S H; Zhou, L; Chen, Z J; Liu, K; Yang, G C; Hu, G; He, G C; You, A Q

2015-03-30

The ATP-binding cassette (ABC) transporters belong to a large superfamily of proteins that have important physiological functions in all living organisms. In insects, ABC transporters have important functions in the transport of molecules, and are also involved in insecticide resistance, metabolism, and development. In this study, the Nilaparvata lugens Stal (Hemiptera: Delphacidae) ABCG (NlABCG) gene was identified and characterized. The complete mRNA sequence of NlABCG was 2608-bp long, with an open reading frame of 2064 bp encoding a protein comprised of 687 amino acids. The conserved regions include three N-glycosylation and 34 phosphorylation sites, as well as seven transmembrane domains. The amino acid identity with the closely related species Acyrthosiphon pisum was 42.8%. Developmental expression analysis using quantitative real-time reverse transcriptase PCR suggested that the NlABCG transcript was expressed at all developmental stages of N. lugens. The lowest expression of NlABCG was in the 1st instar, and levels increased with larval growth. The transcript profiles of NlABCG were analyzed in various tissues from a 5th instar nymph, and the highest expression was observed in the midgut. These results suggest that the sequence, characteristics, and expression of NlABCG are highly conserved, and basic information is provided for its functional analysis.

'Drawing' a Molecular Portrait of CIN and Cervical Cancer: a Review of Genome-Wide Molecular Profiling Data.

PubMed

Kurmyshkina, Olga V; Kovchur, Pavel I; Volkova, Tatyana O

2015-01-01

In this review we summarize the results of studies employing high-throughput methods of profiling of HPV-associated cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancers at key intracellular regulatory levels to demonstrate the unique identity of the landscape of molecular changes underlying this oncopathology, and to show how these changes are related to the 'natural history' of cervical cancer progression and the formation of clinically significant properties of tumors. A step-wise character of cervical cancer progression is a morphologically well-described fact and, as evidenced by genome-wide screenings, it is indeed the consistent change of the molecular profiles of HPV-infected epithelial cells through which they progressively acquire the phenotypic hallmarks of cancerous cells. In this sense, CIN/cervical cancer is a unique model for studying the driving forces and mechanisms of carcinogenesis. Recent research has allowed definition of the whole-genome spectrum of both random and regular molecular alterations, as well as changes either common to processes of carcinogenesis or specific for cervical cancer. Despite the existence of questions that are still to be investigated, these findings are of great value for the future development of approaches for the diagnostics and treatment of cervical neoplasms.

Undergraduate HBCU Student Summer Training Program for Developing Nanomedicines to Treat Prostate Cancers

DTIC Science & Technology

2017-10-01

pancreatic cancer cells. 3. Sequoyah Bennett Sequoyah worked in the lab of Dr. Surinder Batra, Department of Biochemistry and Molecular Biology , College...the lab of Dr. Kaustubh Datta, Department of Biochemistry and Molecular Biology at the University of Nebraska Medical Center. During that time, Ciera...following the therapeutic intervention or prostate cancer. Furthermore, she learned the basic cell culture and molecular biology techniques. (2016) 1

Molecular heterogeneity at the network level: high-dimensional testing, clustering and a TCGA case study | Office of Cancer Genomics

Cancer.gov

Motivation: Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging.

Quality Assurance Program for Molecular Medicine Laboratories

PubMed Central

Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B

2013-01-01

Background: Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. Methods: We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Results: Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Conclusion: Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level. PMID:23865028

Quality assurance program for molecular medicine laboratories.

PubMed

Hajia, M; Safadel, N; Samiee, S Mirab; Dahim, P; Anjarani, S; Nafisi, N; Sohrabi, A; Rafiee, M; Sabzavi, F; Entekhabi, B

2013-01-01

Molecular diagnostic methods have played and continuing to have a critical role in clinical laboratories in recent years. Therefore, standardization is an evolutionary process that needs to be upgrade with increasing scientific knowledge, improvement of the instruments and techniques. The aim of this study was to design a quality assurance program in order to have similar conditions for all medical laboratories engaging with molecular tests. We had to design a plan for all four elements; required space conditions, equipments, training, and basic guidelines. Necessary guidelines was prepared and confirmed by the launched specific committee at the Health Reference Laboratory. Several workshops were also held for medical laboratories directors and staffs, quality control manager of molecular companies, directors and nominees from universities. Accreditation of equipments and molecular material was followed parallel with rest of program. Now we are going to accredit medical laboratories and to evaluate the success of the program. Accreditation of medical laboratory will be succeeding if its basic elements are provided in advance. Professional practice guidelines, holding training and performing accreditation the molecular materials and equipments ensured us that laboratories are aware of best practices, proper interpretation, limitations of techniques, and technical issues. Now, active external auditing can improve the applied laboratory conditions toward the defined standard level.

A cascade reaction network mimicking the basic functional steps of adaptive immune response

NASA Astrophysics Data System (ADS)

Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

2015-10-01

Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

Developing a Model of Compulsory Basic Education Completion Acceleration in Support of Millennium Development Goals in Magelang, Indonesia

ERIC Educational Resources Information Center

Sukarno; Haryati, Sri

2015-01-01

This article reports Year One of a two-year study to develop a model to accelerate compulsory basic education completion toward Millennium Development Goals (MDGs) in Magelang, Indonesia. The study focuses on five issues: (1) profile of MDGs in Magelang, (2) achievement of MDGs, (3) problems in MDGs implementation, (4) model of compulsary basic…

Can the Problem of Illiteracy Be Solved? A View Based on AVC Edmonton's Adult Basic Education Program.

ERIC Educational Resources Information Center

Burghardt, F. F.

An estimated 850,000 Canadian adults lack basic literacy skills. An examination of the profile and achievements of the students enrolled in the literacy education program at the Alberta Vocational Centre in Edmonton indicates that like the many other types in the broad range of adult literacy programs, the highly structured nature of the Edmonton…

Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine.

PubMed

Subbiah, Vivek; Wagner, Michael J; McGuire, Mary F; Sarwari, Nawid M; Devarajan, Eswaran; Lewis, Valerae O; Westin, Shanon; Kato, Shumei; Brown, Robert E; Anderson, Pete

2015-12-01

Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis. In Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2-16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy. Relapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized therapies for cancer. Methods for such profiling are evolving and need to be refined to better assist clinicians in making treatment decisions based on the large amount of data that results from this type of testing. Further research in this area is warranted.

Theoretical Compton profile anisotropies in molecules and solids. IV. Parallel--perpendicular anisotropies in alkali fluoride molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matcha, R.L.; Pettitt, B.M.; Ramirez, B.I.

1979-07-15

Calculations of Compton profiles and parallel--perpendicular anisotropies in alkali fluorides are presented and analyzed in terms of molecular charge distributions and wave function character. It is found that the parallel profile associated with the valence pi orbital is the principal factor determining the relative shapes of the total profile anisotropies in the low momentum region.

Understanding the Atom and Relevant Misconceptions: Students' Profiles in Relation to Three Cognitive Variables

ERIC Educational Resources Information Center

Papageorgiou, George; Markos, Angelos; Zarkadis, Nikolaos

2016-01-01

This work investigates the formation of particular student profiles based on of their ideas relating to basic characteristics of the atom. Participants were secondary students of 8th, 10th and 12th grades from Northern Greece (n = 421), with specific cohort characteristics e.g. age, grade and class curriculum, and individual differences, e.g.…

Vocational Guidance for the Deaf; A Classified Guide to the Basic Requirements for Occupations Open to the Profoundly Deaf.

ERIC Educational Resources Information Center

Montgomery, G.W.G.

Published in Britain for use by counselors and placement officials, the book offers a systematic attack on occupational placement problems of the prelingually deaf. The system is based on a vocational guidance profile, which is developed from intelligence and achievement test scores. The vocational guidance profile is explained, and occupational…

CGDM: collaborative genomic data model for molecular profiling data using NoSQL.

PubMed

Wang, Shicai; Mares, Mihaela A; Guo, Yi-Ke

2016-12-01

High-throughput molecular profiling has greatly improved patient stratification and mechanistic understanding of diseases. With the increasing amount of data used in translational medicine studies in recent years, there is a need to improve the performance of data warehouses in terms of data retrieval and statistical processing. Both relational and Key Value models have been used for managing molecular profiling data. Key Value models such as SeqWare have been shown to be particularly advantageous in terms of query processing speed for large datasets. However, more improvement can be achieved, particularly through better indexing techniques of the Key Value models, taking advantage of the types of queries which are specific for the high-throughput molecular profiling data. In this article, we introduce a Collaborative Genomic Data Model (CGDM), aimed at significantly increasing the query processing speed for the main classes of queries on genomic databases. CGDM creates three Collaborative Global Clustering Index Tables (CGCITs) to solve the velocity and variety issues at the cost of limited extra volume. Several benchmarking experiments were carried out, comparing CGDM implemented on HBase to the traditional SQL data model (TDM) implemented on both HBase and MySQL Cluster, using large publicly available molecular profiling datasets taken from NCBI and HapMap. In the microarray case, CGDM on HBase performed up to 246 times faster than TDM on HBase and 7 times faster than TDM on MySQL Cluster. In single nucleotide polymorphism case, CGDM on HBase outperformed TDM on HBase by up to 351 times and TDM on MySQL Cluster by up to 9 times. The CGDM source code is available at https://github.com/evanswang/CGDM. y.guo@imperial.ac.uk. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins

NASA Astrophysics Data System (ADS)

Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

2016-03-01

The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm- 1 and 1545 cm- 1, respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

A study of the effect of a boundary layer profile on the dynamic response and acoustic radiation of flat panels. Ph.D. Thesis - Virginia Univ.

NASA Technical Reports Server (NTRS)

Mixson, J. S.

1973-01-01

The response of a thin, elastic plate to a harmonic force which drives the plate from below and a compressible air stream with a viscous boundary layer flowing parallel to the upper surface along the length was investigated. Equations governing the forced response of the coupled plate-aerodynamic system are derived along with appropriate boundary conditions. Calculations of basic solution parameters for a linear velocity profile and for a Blasius profile showed that the same system response could be obtained from each profile if appropriate values of boundary layer thickness were chosen for each profile.

Current molecular profile of juvenile nasopharyngeal angiofibroma: First comprehensive study from India.

PubMed

Pandey, Praveen; Mishra, Anupam; Tripathi, Ashoak Mani; Verma, Veerendra; Trivedi, Ritu; Singh, Hitendra Prakash; Kumar, Sunil; Patel, Brijesh; Singh, Vinay; Pandey, Shivani; Pandey, Amita; Mishra, Subhash Chandra

2017-03-01

An attempt is made to analyze the molecular behavior of juvenile nasopharyngeal angiofibroma (JNA). Case Series METHODS: Quantification of mRNAs expression was undertaken through real-time polymerase chain reaction in JNA (9-24) samples for VEGF-A, basic fibroblast growth factor (b-FGF), platelet-derived growth factor PDGF-A, KIT proto-oncogene receptor tyrosine kinase (c-Kit), Avian myelomatosis viral oncogene homolog (c-Myc), Harvey rat sarcoma viral oncogene homolog (H-Ras), tumor suppressor gene TP53, and androgen receptor and interleukin 6 (IL-6). The β-catenin expression was evaluated by western blot in 16 samples. Nasal polyp was taken as control. A significantly increased (P < 0.01) expression of c-myc, VEGFA, bFGF, PDGFA, c-kit, and TP53 was seen, along with enhanced expression of β-catenin. A massive enhancement of H-Ras expression was seen for the first time. Androgen receptor expression was no different, whereas IL-6 despite showing upregulation trend was not significant. The enhanced expressions of various markers suggest their potential role in JNA. Although the biological significance of c-kit, c-myc, and one of the novel markers H-Ras has yet to be defined, their significant expression may have a therapeutic importance. NA. Laryngoscope, 127:E100-E106, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Characterisation of CDKL5 Transcript Isoforms in Human and Mouse

PubMed Central

Dando, Owen; Landsberger, Nicoletta; Kilstrup-Nielsen, Charlotte; Kind, Peter C.; Bailey, Mark E. S.; Cobb, Stuart R.

2016-01-01

Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3’-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders. PMID:27315173

Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.

PubMed

Hector, Ralph D; Dando, Owen; Landsberger, Nicoletta; Kilstrup-Nielsen, Charlotte; Kind, Peter C; Bailey, Mark E S; Cobb, Stuart R

2016-01-01

Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders.

Basic or extended urine sampling to analyse urine production?

PubMed

Denys, Marie-Astrid; Kapila, Vansh; Weiss, Jeffrey; Goessaert, An-Sofie; Everaert, Karel

2017-09-01

Frequency volume charts are valuable tools to objectify urine production in patients with nocturia, enuresis or nocturnal incontinence. Analyses of daytime and nighttime urine (=basic collection) or analyses of urine samples collected every 3 h (=extended collection) extend this evaluation by describing circadian patterns of water and solute diuresis (=renal function profiles). To assess intra-individual correlation and agreement between renal function profiles provided using basic and extended urine collections, and using two extended urine collections. To create a short-form of the extended collection. This prospective observational study was executed at Ghent University Hospital, Belgium. Study participation was open for anyone visiting the hospital. Participants collected one basic and two extended 24-h urine collections. Urinary levels of osmolality, sodium and creatinine were determined. There was a moderate to strong correlation between results of basic and extended urinalyses. Comparing both extended urinalyses showed a moderate correlation between the eight individual samples and a weak to strong correlation between the mean daytime and nighttime values of renal functions. Different samples could be considered as most representative for mean daytime values, while all samples collected between 03 and 05am showed the highest agreement with mean nighttime values of renal function. Since there is a good correlation and agreement between basic and extended urine collections to study the mechanisms underlying urine production, the choice of urine sampling method to evaluate urine production depends on the purpose. A nighttime-only urine sample collected between 03 and 05am may be the most practical approach. © 2017 Wiley Periodicals, Inc.

Intra- and intermolecular effects on the Compton profile of the ionic liquid 1,3-dimethylimidazolium chloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koskelo, J., E-mail: jaakko.koskelo@helsinki.fi; Juurinen, I.; Ruotsalainen, K. O.

2014-12-28

We present a comprehensive simulation study on the solid-liquid phase transition of the ionic liquid 1,3-dimethylimidazolium chloride in terms of the changes in the atomic structure and their effect on the Compton profile. The structures were obtained by using ab initio molecular dynamics simulations. Chosen radial distribution functions of the liquid structure are presented and found generally to be in good agreement with previous ab initio molecular dynamics and neutron scattering studies. The main contributions to the predicted difference Compton profile are found to arise from intermolecular changes in the phase transition. This prediction can be used for interpreting futuremore » experiments.« less

Wall-collision line broadening of molecular oxygen within nanoporous materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Can T.; Lewander, Maerta; Andersson-Engels, Stefan

2011-10-15

Wall-collision broadening of near-infrared absorption lines of molecular oxygen confined in nanoporous zirconia is studied by employing high-resolution diode-laser spectroscopy. The broadening is studied for pores of different sizes under a range of pressures, providing new insights on how wall collisions and intermolecular collisions influence the total spectroscopic line profile. The pressure series show that wall-collision broadening is relatively more prominent under reduced pressures, enabling sensitive means to probe pore sizes of porous materials. In addition, we show that the total wall-collision-broadened profile strongly deviates from a Voigt profile and that wall-collision broadening exhibits an additive-like behavior to the pressuremore » and Doppler broadening.« less

Studying bacteria in respiratory specimens by using conventional and molecular microbiological approaches

PubMed Central

Rogers, Geraint B; Daniels, Thomas WV; Tuck, Andrew; Carroll, Mary P; Connett, Gary J; David, Gondi JP; Bruce, Kenneth D

2009-01-01

Background Drawing from previous studies, the traditional routine diagnostic microbiology evaluation of samples from chronic respiratory conditions may provide an incomplete picture of the bacteria present in airways disease. Here, the aim was to determine the extent to which routine diagnostic microbiology gave a different assessment of the species present in sputa when analysed by using culture-independent assessment. Methods Six different media used in routine diagnostic microbiology were inoculated with sputum from twelve patients. Bacterial growth on these plates was harvested and both RNA and DNA extracted. DNA and RNA were also extracted directly from the same sample of sputum. All nucleic acids served as templates for PCR and reverse transcriptase-PCR amplification of "broad range" bacterial 16S rRNA gene regions. The regions amplified were separated by Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling and compared to assess the degree of overlap between approaches. Results A mean of 16.3 (SD 10.0) separate T-RF band lengths in the profiles from each sputum sample by Direct Molecular Analysis, with a mean of 8.8 (SD 5.8) resolved by DNA profiling and 13.3 (SD 8.0) resolved by RNA profiling. In comparison, 8.8 (SD 4.4) T-RF bands were resolved in profiles generated by Culture-derived Molecular Analysis. There were a total of 184 instances of T-RF bands detected in the direct sputum profiles but not in the corresponding culture-derived profiles, representing 83 different T-RF band lengths. Amongst these were fifteen instances where the T-RF band represented more than 10% of the total band volume (with a mean value of 23.6%). Eight different T-RF band lengths were resolved as the dominant band in profiles generated directly from sputum. Of these, only three were detected in profiles generated from the corresponding set of cultures. Conclusion Due to their focus on isolation of a small group of recognised pathogens, the use of culture-dependent methods to analyse samples from chronic respiratory infections can provide a restricted understanding of the bacterial species present. The use of a culture-independent molecular approach here identifies that there are many bacterial species in samples from CF and COPD patients that may be clinically relevant. PMID:19368727

Balancing volume and duration of information consumption by physicians: The case of health information exchange in critical care.

PubMed

Politi, Liran; Codish, Shlomi; Sagy, Iftach; Fink, Lior

2017-07-01

The realization of the potential benefits of health information exchange systems (HIEs) for emergency departments (EDs) depends on the way these systems are actually used. The attributes of volume of information and duration of information processing are important for the study of HIE use patterns in the ED, as cognitive load and time constraints may result in a trade-off between these attributes. Experts and non-experts often use different problem-solving strategies, which may be consequential for their system use patterns. Little previous research focuses on the trade-off between volume and duration of system use or on the factors that affect it, including user expertise. This study aims at exploring the trade-off of volume and duration of use, examining whether this relationship differs between experts and non-experts, and identifying factors that are associated with use patterns characterized by volume and duration. The research objectives are pursued in the context of critically-ill patients, treated at a busy ED in the period 2010-2012. The primary source of internal and external data is an HIE linked to 14 hospitals, over 1300 clinics, and other clinical facilities. We define four use profiles based on the attributes of duration and volume: quick and basic, quick and deep, slow and basic, and slow and deep. The volume and duration of use are computed using HIE log files as the number of screens and the time per screen, respectively. Each session is then classified into a specific profile based on distances from predefined profile centroids. Experts are physicians that are board-certified in emergency medicine. We test the distribution of use profiles and their associations with multiple variables that describe the patient, physician, situation, information available in the HIE system, and use dynamics within the encounter. The quick and basic profile is the most prevalent. While available admission summaries are associated with quick and basic use, lab and imaging results are associated with slower or deeper use. Physicians who are the first to use the system or are sole users during an encounter are less inclined to quick and deep use. These effects are intensified for experts. A trade-off between volume and duration is identified. While system use is overall similar for experts and non-experts, the circumstances in which a certain profile is more likely to be observed vary across these two groups. Information availability and multiple-physician dynamics within the encounter emerge as important for the prediction of use profiles. The findings of this study provide implications for the design, implementation, and research of HIE use. Copyright © 2017 Elsevier Inc. All rights reserved.

The rise of genomic profiling in ovarian cancer

PubMed Central

Previs, Rebecca A.; Sood, Anil K.; Mills, Gordon B.; Westin, Shannon N.

2017-01-01

Introduction Next-generation sequencing and advances in ‘omics technology have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers. Areas covered Once characterized only by histologic appearance and clinical behavior, we now understand many of the molecular phenotypes that underlie the different ovarian cancer subtypes. While the current approach to treatment involves standard cytotoxic therapies after cytoreductive surgery for all ovarian cancers regardless of histologic or molecular characteristics, focus has shifted beyond a ‘one size fits all’ approach to ovarian cancer. Expert commentary Genomic profiling offers potentially ‘actionable’ opportunities for development of targeted therapies and a more individualized approach to treatment with concomitant improved outcomes and decreased toxicity. PMID:27828713

Human papillomavirus molecular biology.

PubMed

Harden, Mallory E; Munger, Karl

Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluating cell lines as tumour models by comparison of genomic profiles

PubMed Central

Domcke, Silvia; Sinha, Rileen; Levine, Douglas A.; Sander, Chris; Schultz, Nikolaus

2013-01-01

Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types. PMID:23839242

New diagnostic methods for laser plasma- and microwave-enhanced combustion

PubMed Central

Miles, Richard B; Michael, James B; Limbach, Christopher M; McGuire, Sean D; Chng, Tat Loon; Edwards, Matthew R; DeLuca, Nicholas J; Shneider, Mikhail N; Dogariu, Arthur

2015-01-01

The study of pulsed laser- and microwave-induced plasma interactions with atmospheric and higher pressure combusting gases requires rapid diagnostic methods that are capable of determining the mechanisms by which these interactions are taking place. New rapid diagnostics are presented here extending the capabilities of Rayleigh and Thomson scattering and resonance-enhanced multi-photon ionization (REMPI) detection and introducing femtosecond laser-induced velocity and temperature profile imaging. Spectrally filtered Rayleigh scattering provides a method for the planar imaging of temperature fields for constant pressure interactions and line imaging of velocity, temperature and density profiles. Depolarization of Rayleigh scattering provides a measure of the dissociation fraction, and multi-wavelength line imaging enables the separation of Thomson scattering from Rayleigh scattering. Radar REMPI takes advantage of high-frequency microwave scattering from the region of laser-selected species ionization to extend REMPI to atmospheric pressures and implement it as a stand-off detection method for atomic and molecular species in combusting environments. Femtosecond laser electronic excitation tagging (FLEET) generates highly excited molecular species and dissociation through the focal zone of the laser. The prompt fluorescence from excited molecular species yields temperature profiles, and the delayed fluorescence from recombining atomic fragments yields velocity profiles. PMID:26170432

Implications of publicly available genomic data resources in searching for therapeutic targets of obesity and type 2 diabetes.

PubMed

Jung, Sungwon

2018-04-20

Obesity and type 2 diabetes (T2D) are two major conditions that are related to metabolic disorders and affect a large population. Although there have been significant efforts to identify their therapeutic targets, few benefits have come from comprehensive molecular profiling. This limited availability of comprehensive molecular profiling of obesity and T2D may be due to multiple challenges, as these conditions involve multiple organs and collecting tissue samples from subjects is more difficult in obesity and T2D than in other diseases, where surgical treatments are popular choices. While there is no repository of comprehensive molecular profiling data for obesity and T2D, multiple existing data resources can be utilized to cover various aspects of these conditions. This review presents studies with available genomic data resources for obesity and T2D and discusses genome-wide association studies (GWAS), a knockout (KO)-based phenotyping study, and gene expression profiles. These studies, based on their assessed coverage and characteristics, can provide insights into how such data can be utilized to identify therapeutic targets for obesity and T2D.

Biochemical and Molecular Analysis of Some Commercial Samples of Chilli Peppers from Mexico

PubMed Central

Troconis-Torres, Ivonne Guadalupe; Rojas-López, Marlon; Hernández-Rodríguez, César; Villa-Tanaca, Lourdes; Maldonado-Mendoza, Ignacio Eduardo; Dorantes-Álvarez, Lidia; Tellez-Medina, Darío; Jaramillo-Flores, María Eugenia

2012-01-01

The genus Capsicum provides antioxidant compounds, such as phenolics and carotenoids, into the diet. In Mexico, there is a wide diversity of species and varieties of chilli peppers, a fruit which has local cultural and gastronomic importance. In the present study, the relationship of the carotenoid and phenolic profiles with the RAPD fingerprint of three different commercial cultivars of chilli peppers of seven regions of Mexico was investigated. Through RAPD, the species of chilli were differentiated by means of different primers (OPE-18, MFG-17, MFG-18, C51, and C52). The genetic distance found with OPE 18 was in the order of 2.6. The observed differences were maintained when the chromatographic profile of carotenoids, and the molecular markers were analyzed, which suggest a close relationship between carotenoids and the genetic profile. While the chromatographic profile of phenols and the molecular markers were unable to differentiate between genotypes of chilli peppers. In addition, by using infrared spectroscopy and statistical PCA, differences explained by geographic origin were found. Thus, this method could be an alternative for identification of chilli species with respect to their geographic origin. PMID:22665993

Transition Pathway and Its Free-Energy Profile: A Protocol for Protein Folding Simulations

PubMed Central

Lee, In-Ho; Kim, Seung-Yeon; Lee, Jooyoung

2013-01-01

We propose a protocol that provides a systematic definition of reaction coordinate and related free-energy profile as the function of temperature for the protein-folding simulation. First, using action-derived molecular dynamics (ADMD), we investigate the dynamic folding pathway model of a protein between a fixed extended conformation and a compact conformation. We choose the pathway model to be the reaction coordinate, and the folding and unfolding processes are characterized by the ADMD step index, in contrast to the common a priori reaction coordinate as used in conventional studies. Second, we calculate free-energy profile as the function of temperature, by employing the replica-exchange molecular dynamics (REMD) method. The current method provides efficient exploration of conformational space and proper characterization of protein folding/unfolding dynamics from/to an arbitrary extended conformation. We demonstrate that combination of the two simulation methods, ADMD and REMD, provides understanding on molecular conformational changes in proteins. The protocol is tested on a small protein, penta-peptide of met-enkephalin. For the neuropeptide met-enkephalin system, folded, extended, and intermediate sates are well-defined through the free-energy profile over the reaction coordinate. Results are consistent with those in the literature. PMID:23917881

Biochemical and molecular analysis of some commercial samples of chilli peppers from Mexico.

PubMed

Troconis-Torres, Ivonne Guadalupe; Rojas-López, Marlon; Hernández-Rodríguez, César; Villa-Tanaca, Lourdes; Maldonado-Mendoza, Ignacio Eduardo; Dorantes-Álvarez, Lidia; Tellez-Medina, Darío; Jaramillo-Flores, María Eugenia

2012-01-01

The genus Capsicum provides antioxidant compounds, such as phenolics and carotenoids, into the diet. In Mexico, there is a wide diversity of species and varieties of chilli peppers, a fruit which has local cultural and gastronomic importance. In the present study, the relationship of the carotenoid and phenolic profiles with the RAPD fingerprint of three different commercial cultivars of chilli peppers of seven regions of Mexico was investigated. Through RAPD, the species of chilli were differentiated by means of different primers (OPE-18, MFG-17, MFG-18, C51, and C52). The genetic distance found with OPE 18 was in the order of 2.6. The observed differences were maintained when the chromatographic profile of carotenoids, and the molecular markers were analyzed, which suggest a close relationship between carotenoids and the genetic profile. While the chromatographic profile of phenols and the molecular markers were unable to differentiate between genotypes of chilli peppers. In addition, by using infrared spectroscopy and statistical PCA, differences explained by geographic origin were found. Thus, this method could be an alternative for identification of chilli species with respect to their geographic origin.

Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory

ERIC Educational Resources Information Center

Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

2010-01-01

A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…

21 CFR 177.1440 - 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1440 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10... may be safely used as articles or components of articles intended for use in producing, manufacturing...

21 CFR 177.1440 - 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1440 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10... may be safely used as articles or components of articles intended for use in producing, manufacturing...

A Cartoon in One Dimension of the Hydrogen Molecular Ion

ERIC Educational Resources Information Center

Dutta, Sourav; Ganguly, Shreemoyee; Dutta-Roy, Binayak

2008-01-01

To illustrate the basic methodology involved in the quantum mechanics of molecules, a one-dimensional caricature of the hydrogen molecular ion (H[superscript +][subscript 2]) is presented, which is exactly solvable, in the Born-Oppenheimer approximation, in terms of elementary functions. The purpose of the exercise is to elucidate in a simple…

BIOPS Interactive: An e-Learning Platform Focused on Protein Structure and DNA

ERIC Educational Resources Information Center

Pontelli, Enrico; Pinto, Jorge; Qin, Xiaoxiao; He, Jing; Bevan, David; MacCuish, Norah; MacCuish, John; Chapman, Mitch; Moreland, David

2009-01-01

One of the difficulties in teaching basic molecular biology concepts to the students with little biological background is the lack of hands-on exercises that combines the challenges of the concepts with visualization and immediate feedback. BIOPS Interactive is a web-based interactive learning environment for molecular biology that complements…

Neurobiological Mechanisms for the Regulation of Mammalian Sleep-Wake Behavior: Reinterpretation of Historical Evidence and Inclusion of Contemporary Cellular and Molecular Evidence

PubMed Central

Datta, Subimal; MacLean, Robert Ross

2007-01-01

At its most basic level, the function of mammalian sleep can be described as a restorative process of the brain and body; recently, however, progressive research has revealed a host of vital functions to which sleep is essential. Although many excellent reviews on sleep behavior have been published, none have incorporated contemporary studies examining the molecular mechanisms that govern the various stages of sleep. Utilizing a holistic approach, this review is focused on the basic mechanisms involved in the transition from wakefulness, initiation of sleep and the subsequent generation of slow-wave sleep and rapid eye movement (REM) sleep. Additionally, using recent molecular studies and experimental evidence that provides a direct link to sleep as a behavior, we have developed a new model, the Cellular-Molecular-Network model, explaining the mechanisms responsible for regulating REM sleep. By analyzing the fundamental neurobiological mechanisms responsible for the generation and maintenance of sleep-wake behavior in mammals, we intend to provide a broader understanding of our present knowledge in the field of sleep research. PMID:17445891

Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice.

PubMed

Schraut, K G; Jakob, S B; Weidner, M T; Schmitt, A G; Scholz, C J; Strekalova, T; El Hajj, N; Eijssen, L M T; Domschke, K; Reif, A; Haaf, T; Ortega, G; Steinbusch, H W M; Lesch, K P; Van den Hove, D L

2014-10-21

The serotonin transporter gene (5-HTT/SLC6A4)-linked polymorphic region has been suggested to have a modulatory role in mediating effects of early-life stress exposure on psychopathology rendering carriers of the low-expression short (s)-variant more vulnerable to environmental adversity in later life. The underlying molecular mechanisms of this gene-by-environment interaction are not well understood, but epigenetic regulation including differential DNA methylation has been postulated to have a critical role. Recently, we used a maternal restraint stress paradigm of prenatal stress (PS) in 5-HTT-deficient mice and showed that the effects on behavior and gene expression were particularly marked in the hippocampus of female 5-Htt+/- offspring. Here, we examined to which extent these effects are mediated by differential methylation of DNA. For this purpose, we performed a genome-wide hippocampal DNA methylation screening using methylated-DNA immunoprecipitation (MeDIP) on Affymetrix GeneChip Mouse Promoter 1.0 R arrays. Using hippocampal DNA from the same mice as assessed before enabled us to correlate gene-specific DNA methylation, mRNA expression and behavior. We found that 5-Htt genotype, PS and their interaction differentially affected the DNA methylation signature of numerous genes, a subset of which showed overlap with the expression profiles of the corresponding transcripts. For example, a differentially methylated region in the gene encoding myelin basic protein (Mbp) was associated with its expression in a 5-Htt-, PS- and 5-Htt × PS-dependent manner. Subsequent fine-mapping of this Mbp locus linked the methylation status of two specific CpG sites to Mbp expression and anxiety-related behavior. In conclusion, hippocampal DNA methylation patterns and expression profiles of female prenatally stressed 5-Htt+/- mice suggest that distinct molecular mechanisms, some of which are promoter methylation-dependent, contribute to the behavioral effects of the 5-Htt genotype, PS exposure and their interaction.

Saturn's equatorial jet structure from Cassini/ISS

NASA Astrophysics Data System (ADS)

García-Melendo, Enrique; Legarreta, Jon; Sánchez-Lavega, Agustín.; Pérez-Hoyos, Santiago; Hueso, Ricardo

2010-05-01

Detailed wind observations of the equatorial regions of the gaseous giant planets, Jupiter and Saturn, are crucial for understanding the basic problem of the global circulation and obtaining new detailed information on atmospheric phenomena. In this work we present high resolution data of Saturn's equatorial region wind profile from Cassini/ISS images. To retrieve wind measurements we applied an automatic cross correlator to image pairs taken by Cassini/ISS with the MT1, MT2, MT3 filters centred at the respective three methane absorbing bands of 619nm, 727nm, and 889nm, and with the adjacent continuum CB1, CB2, and CB3 filters. We obtained a complete high resolution coverage of Saturn's wind profile in the equatorial region. The equatorial jet displays an overall symmetric structure similar to that shown the by same region in Jupiter. This result suggests that, in accordance to some of the latest compressible atmosphere computer models, probably global winds in gaseous giants are deeply rooted in the molecular hydrogen layer. Wind profiles in the methane absorbing bands show the effect of strong vertical shear, ~40m/s per scale height, confirming previous results and an important decay in the wind intensity since the Voyager era (~100 m/s in the continuum and ~200 m/s in the methane absorbing band). We also report the discovery of a new feature, a very strong and narrow jet on the equator, about only 5 degrees wide, that despite the vertical shear maintains its intensity (~420 m/s) in both, the continuum and methane absorbing band filters. Acknowledgements: Work supported by the Spanish MICIIN AYA2009-10701 with FEDER and Grupos Gobierno Vasco IT-464-07.

GEPSI: A Gene Expression Profile Similarity-Based Identification Method of Bioactive Components in Traditional Chinese Medicine Formula.

PubMed

Zhang, Baixia; He, Shuaibing; Lv, Chenyang; Zhang, Yanling; Wang, Yun

2018-01-01

The identification of bioactive components in traditional Chinese medicine (TCM) is an important part of the TCM material foundation research. Recently, molecular docking technology has been extensively used for the identification of TCM bioactive components. However, target proteins that are used in molecular docking may not be the actual TCM target. For this reason, the bioactive components would likely be omitted or incorrect. To address this problem, this study proposed the GEPSI method that identified the target proteins of TCM based on the similarity of gene expression profiles. The similarity of the gene expression profiles affected by TCM and small molecular drugs was calculated. The pharmacological action of TCM may be similar to that of small molecule drugs that have a high similarity score. Indeed, the target proteins of the small molecule drugs could be considered TCM targets. Thus, we identified the bioactive components of a TCM by molecular docking and verified the reliability of this method by a literature investigation. Using the target proteins that TCM actually affected as targets, the identification of the bioactive components was more accurate. This study provides a fast and effective method for the identification of TCM bioactive components.

GEPSI: A Gene Expression Profile Similarity-Based Identification Method of Bioactive Components in Traditional Chinese Medicine Formula

PubMed Central

Zhang, Baixia; He, Shuaibing; Lv, Chenyang; Zhang, Yanling

2018-01-01

The identification of bioactive components in traditional Chinese medicine (TCM) is an important part of the TCM material foundation research. Recently, molecular docking technology has been extensively used for the identification of TCM bioactive components. However, target proteins that are used in molecular docking may not be the actual TCM target. For this reason, the bioactive components would likely be omitted or incorrect. To address this problem, this study proposed the GEPSI method that identified the target proteins of TCM based on the similarity of gene expression profiles. The similarity of the gene expression profiles affected by TCM and small molecular drugs was calculated. The pharmacological action of TCM may be similar to that of small molecule drugs that have a high similarity score. Indeed, the target proteins of the small molecule drugs could be considered TCM targets. Thus, we identified the bioactive components of a TCM by molecular docking and verified the reliability of this method by a literature investigation. Using the target proteins that TCM actually affected as targets, the identification of the bioactive components was more accurate. This study provides a fast and effective method for the identification of TCM bioactive components. PMID:29692857

Early molecular correlates of adverse events following yellow fever vaccination

PubMed Central

Chan, Candice Y.Y.; Chan, Kuan Rong; Chua, Camillus J.H.; nur Hazirah, Sharifah; Ghosh, Sujoy; Ooi, Eng Eong; Low, Jenny G.

2017-01-01

The innate immune response shapes the development of adaptive immunity following infections and vaccination. However, it can also induce symptoms such as fever and myalgia, leading to the possibility that the molecular basis of immunogenicity and reactogenicity of vaccination are inseparably linked. To test this possibility, we used the yellow fever live-attenuated vaccine (YFLAV) as a model to study the molecular correlates of reactogenicity or adverse events (AEs). We analyzed the outcome of 68 adults who completed a YFLAV clinical trial, of which 43 (63.2%) reported systemic AEs. Through whole-genome profiling of blood collected before and after YFLAV dosing, we observed that activation of innate immune genes at day 1, but not day 3 after vaccination, was directly correlated with AEs. These findings contrast with the gene expression profile at day 3 that we and others have previously shown to be correlated with immunogenicity. We conclude that although the innate immune response is a double-edged sword, its expression that induces AEs is temporally distinct from that which engenders robust immunity. The use of genomic profiling thus provides molecular insights into the biology of AEs that potentially forms a basis for the development of safer vaccines. PMID:28978802

Physics for excited neutrons

NASA Astrophysics Data System (ADS)

Cartlidge, Edwin

2017-01-01

Some scientists claim they can control genetically engineered neurons using magnetic fields. Have they and the high-profile journals that published their research failed to understand basic physics? Edwin Cartlidge investigates

Gene expression profiling of breast cancer cell lines treated with proton and electron radiations.

PubMed

Bravatà, Valentina; Minafra, Luigi; Cammarata, Francesco Paolo; Pisciotta, Pietro; Lamia, Debora; Marchese, Valentina; Manti, Lorenzo; Cirrone, Giuseppe Ap; Gilardi, Maria Carla; Cuttone, Giacomo; Forte, Giusi Irma; Russo, Giorgio

2018-06-11

Technological advances in radiation therapy are evolving with the use of hadrons, such as protons, indicated for tumors where conventional radiotherapy does not give significant advantages or for tumors located in sensitive regions, which need the maximum of dose-saving of the surrounding healthy tissues. The genomic response to conventional and non conventional Linear Energy Transfer exposure is a poor investigated topic and became an issue of radiobiological interest. The aim of this work was to analyze and compare molecular responses in term of gene expression profiles, induced by electron and proton irradiation in breast cancer cell lines. We studied the gene expression profiling differences by cDNA microarray activated in response to electron and proton irradiation with different Linear Energy Transfer values, among three breast cell lines (the tumorigenic MCF7 and MDA-MB-231 and the non tumorigenic MCF10A), exposed to the same sub-lethal dose of 9 Gy. Gene expression profiling pathway analyses showed the activation of different signaling and molecular networks in a cell line and radiation type-dependent manner. MCF10A and MDA-MB-231 cell lines were found to induce factors and pathways involved in the immunological process control. Here we describe in a detailed way the gene expression profiling and pathways activated after electron and proton irradiation in breast cancer cells. Summarizing, although specific pathways are activated in a radiation type-dependent manner, each cell line activates overall similar molecular networks in response to both these two types of ionizing radiation. Advances in knowledge: In the era of personalized medicine and breast cancer target-directed intervention, we trust that this study could drive radiation therapy towards personalized treatments, evaluating possible combined treatments, based on the molecular characterization.

Major Upgrades to the AIRS Version-6 Ozone Profile Methodology

NASA Technical Reports Server (NTRS)

Susskind, Joel; Blaisdell, John; Iredell, Lena

2015-01-01

This research is a continuation of part of what was shown at the last AIRS Science Team Meeting in the talk Improved Water Vapor and Ozone Profiles in SRT AIRS Version-6.X and the AIRS February 11, 2015 NetMeeting Further improvements in water vapor and ozone profiles compared to Version-6.AIRS Version-6 was finalized in late 2012 and is now operational. Version-6 contained many significant improvements in retrieval methodology compared to Version-5. However, Version-6 retrieval methodology used for the water vapor profile q(p) and ozone profile O3(p) retrievals is basically unchanged from Version-5, or even from Version-4. Subsequent research has made significant improvements in both water vapor and O3 profiles compared to Version-6. This talk will concentrate on O3 profile retrievals. Improvements in water vapor profile retrievals are given in a separate presentation.

Studies of the electron density in the highest occupied molecular orbitals of PH 3, PF 3 and P(CH 3) 3 by electron momentum spectroscopy and Hartree-Fock, MRSD-CI and DFT calculations

NASA Astrophysics Data System (ADS)

Rolke, J.; Brion, C. E.

1996-06-01

The spherically averaged momentum profiles for the highest occupied molecular orbitals of PF 3 and P(CH 3) 3 have been obtained by electron momentum spectroscopy. The measurements provide a stringent test of basis set effects and the quality of ab-initio methods in the description of these larger molecular systems. As in previous work on the methyl-substituted amines, intuitive arguments fail to predict the correct amount of s- and p-type contributions to the momentum profile while delocalized molecular orbital concepts provide a more adequate description of the HOMOs. The experimental momentum profiles have been compared with theoretical momentum profiles calculated at the level of the target Hartree-Fock approximation with a range of basis sets. New Hartree-Fock calculations are also presented for the HOMO of PH 3 and compared to previously published experimental and theoretical momentum profiles. The experimental momentum profiles have further been compared to calculations at the level of the target Kohn-Sham approximation using density functional theory with the local density approximation and also with gradient corrected (non-local) exchange correlation potentials. In addition, total energies and dipole moments have been calculated for all three molecules by the various theoretical methods and compared to experimental values. Calculated 'density difference maps' show the regions where the HOMO momentum and position electron densities of PF 3 and P(CH 3) 3 change relative to the corresponding HOMO density of PH 3. The results suggest that methyl groups have an electron-attracting effect (relative to H) on the HOMO charge density in trimethyl phosphines. These conclusions are supported by a consideration of dipole moments and the 31P NMR chemical shifts for PH 3, PF 3 and P(CH 3) 3.

Use of mutation profiles to refine the classification of endometrial carcinomas

PubMed Central

Cheang, Maggie CU; Wiegand, Kimberly; Senz, Janine; Tone, Alicia; Yang, Winnie; Prentice, Leah; Tse, Kane; Zeng, Thomas; McDonald, Helen; Schmidt, Amy P.; Mutch, David G.; McAlpine, Jessica N; Hirst, Martin; Shah, Sohrab P; Lee, Cheng-Han; Goodfellow, Paul J; Gilks, C. Blake; Huntsman, David G

2014-01-01

The classification of endometrial carcinomas is based on pathological assessment of tumour cell type; the different cell types (endometrioid, serous, carcinosarcoma, mixed, and clear cell) are associated with distinct molecular alterations. This current classification system for high-grade subtypes, in particular the distinction between high-grade endometrioid (EEC-3) and serous carcinomas (ESC), is limited in its reproducibility and prognostic abilities. Therefore, a search for specific molecular classifiers to improve endometrial carcinoma subclassification is warranted. We performed target enrichment sequencing on 393 endometrial carcinomas from two large cohorts, sequencing exons from the following 9 genes; ARID1A, PPP2R1A, PTEN, PIK3CA, KRAS, CTNNB1, TP53, BRAF and PPP2R5C. Based on this gene panel each endometrial carcinoma subtype shows a distinct mutation profile. EEC-3s have significantly different frequencies of PTEN and TP53 mutations when compared to low-grade endometrioid carcinomas. ESCs and EEC-3s are distinct subtypes with significantly different frequencies of mutations in PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1. From the mutation profiles we were able to identify subtype outliers, i.e. cases diagnosed morphologically as one subtype but with a mutation profile suggestive of a different subtype. Careful review of these diagnostically challenging cases suggested that the original morphological classification was incorrect in most instances. The molecular profile of carcinosarcomas suggests two distinct mutation profiles for these tumours; endometrioid-type (PTEN, PIK3CA, ARID1A, KRAS mutations), and serous-type (TP53 and PPP2R1A mutations). While this nine gene panel does not allow for a purely molecularly based classification of endometrial carcinoma, it may prove useful as an adjunct to morphological classification and serve as an aid in the classification of problematic cases. If used in practice, it may lead to improved diagnostic reproducibility and may also serve to stratify patients for targeted therapeutics. PMID:22653804

Effects of TT8 and HB12 Silencing on the Relations between the Molecular Structures of Alfalfa ( Medicago sativa) Plants and Their Nutritional Profiles and In Vitro Gas Production.

PubMed

Lei, Yaogeng; Hannoufa, Abdelali; Prates, Luciana Louzada; Shi, Haitao; Wang, Yuxi; Biligetu, Bill; Christensen, David; Yu, Peiqiang

2018-06-06

The objective of this study was to investigate the effects of silencing the TT8 and HB12 genes on the nutritive profiles and in vitro gas production of alfalfa in relation to the spectral molecular structures of alfalfa. TT8-silenced (TT8i, n = 5) and HB12-silenced (HB12i, n = 11) alfalfa were generated by RNA interference (RNAi) and grown with nontransgenic wild type controls (WT, n = 4) in a greenhouse. Alfalfa plants were harvested at early-to-mid vegetative stage. Samples were analyzed for their chemical compositions, CNCPS fractions, and in vitro gas production. Correlations and regressions of the nutritional profiles and in vitro gas production with the molecular spectral structures were also determined. The results showed that the transformed alfalfa had higher digestible fiber and lower crude protein with higher proportions of indigestible protein than WT. HB12 RNAi had lower gas production compared with those of the others. Some chemical, CNCPS, and gas-production profiles were closely correlated with spectral structures and could be well predicted from spectral parameters. In conclusion, the RNAi silencing of TT8 and HB12 in alfalfa altered the chemical, CNCPS and gas-production profiles of alfalfa, and such alterations were closely correlated with the inherent spectral structures of alfalfa.

State Test Score Trends through 2008-09, Part 1: Rising Scores on State Tests and NAEP. New Mexico

ERIC Educational Resources Information Center

Center on Education Policy, 2010

2010-01-01

This paper profiles New Mexico's test score trends through 2008-09. Between 2005 and 2009, the percentages of students reaching the proficient level on the state test and the basic level on NAEP (National Assessment of Educational Progress) increased in grade 4 math and grade 8 reading and math. In grade 4 reading, the percentage basic on NAEP …

Comorbidity of Arithmetic and Reading Disorder: Basic Number Processing and Calculation in Children with Learning Impairments

ERIC Educational Resources Information Center

Raddatz, Julia; Kuhn, Jörg-Tobias; Holling, Heinz; Moll, Kristina; Dobel, Christian

2017-01-01

The aim of the present study was to investigate the cognitive profiles of primary school children (age 82-133 months) on a battery of basic number processing and calculation tasks. The sample consisted of four groups matched for age and IQ: arithmetic disorder only (AD; n = 20), reading disorder only (RD; n = 40), a comorbid group (n = 27), and an…

Molecular typing of Vibrio parahaemolyticus isolated from seafood harvested along the south-west coast of India.

PubMed

Bhowmick, P P; Khushiramani, R; Raghunath, P; Karunasagar, I; Karunasagar, I

2008-02-01

Evaluation of protein profiling for typing Vibrio parahaemolyticus using 71 strains isolated from different seafood and comparison with other molecular typing techniques such as random amplified polymorphic DNA analysis (RAPD) and enterobacterial repetitive intergenic consensus sequence (ERIC)-PCR. Three molecular typing methods were used for the typing of 71 V. parahaemolyticus isolates from seafood. RAPD had a discriminatory index (DI) of 0.95, while ERIC-PCR showed a DI of 0.94. Though protein profiling had less discriminatory power, use of this method can be helpful in identifying new proteins which might have a role in establishment in the host or virulence of the organism. The use of protein profiling in combination with other established typing methods such as RAPD and ERIC-PCR generates useful information in the case of V. parahaemolyticus associated with seafood. The study demonstrates the usefulness of nucleic acid and protein-based studies in understanding the relationship between various isolates from seafood.

News & Views Evaluation of Projects for Basic Research of Scientific Instruments in 2008 Completed NSFC Former President Tang Ao-qing Passed Away Professor Tang Aoqing and NSFC Carbon Nanotube Film-Based Speaker Developed in Tsinghua University Dinosaur Footprint Fossils Discovered in Xinjiang New Method for Early Cancer Diagnosis New Progress Achieved by NSFC Project in Basic Research of Black Hole Physics New progress in Organic FET 67 NSFC-RFBR Cooperative Projects Approved for 2008 Spin Configuration and Super-exchange Mechanism in Molecular Magnets Observed NSFC Strengthens its Funding in Wenchuan Concerns Go to Disaster's Impact on Economy and Emergency Response Thirty-seven NSFC-KOSEF Cooperative Projects Approved

NASA Astrophysics Data System (ADS)

2008-01-01

Evaluation of Projects for Basic Research of Scientific Instruments in 2008 Completed NSFC Former President Tang Ao-qing Passed Away Professor Tang Aoqing and NSFC Carbon Nanotube Film-Based Speaker Developed in Tsinghua University Dinosaur Footprint Fossils Discovered in Xinjiang New Method for Early Cancer Diagnosis New Progress Achieved by NSFC Project in Basic Research of Black Hole Physics New progress in Organic FET 67 NSFC-RFBR Cooperative Projects Approved for 2008 Spin Configuration and Super-exchange Mechanism in Molecular Magnets Observed NSFC Strengthens its Funding in Wenchuan Concerns Go to Disaster's Impact on Economy and Emergency Response Thirty-seven NSFC-KOSEF Cooperative Projects Approved

Development of Short-term Molecular Thresholds to Predict Long-term Mouse Liver Tumor Outcomes: Phthalate Case StudyTo be

EPA Science Inventory

Molecular Thresholds for Early Key Events in Liver Tumorgensis: PhthalateCase StudyTriangleShort-term changes in molecular profiles are a central component of strategies to model health effects of environmental chemicals such as phthalates, for which there is widespread human exp...

SSO - Single-Sign-On Profile: Authentication Mechanisms Version 2.0

NASA Astrophysics Data System (ADS)

Taffoni, Giuliano; Schaaf, André; Rixon, Guy; Major, Brian; Taffoni, Giuliano

2017-05-01

Approved client-server authentication mechanisms are described for the IVOA single-sign-on profile: No Authentication; HTTP Basic Authentication; TLS with passwords; TLS with client certificates; Cookies; Open Authentication; Security Assertion Markup Language; OpenID. Normative rules are given for the implementation of these mechanisms, mainly by reference to pre-existing standards. The Authorization mechanisms are out of the scope of this document.

Impact of boiling conditions on the molecular and sensory profile of a vegetable broth.

PubMed

Mougin, Alice; Mauroux, Olivier; Matthey-Doret, Walter; Barcos, Eugenia Maria; Beaud, Fernand; Bousbaine, Ahmed; Viton, Florian; Smarrito-Menozzi, Candice

2015-02-11

Low-pressure cooking has recently been identified as an alternative to ambient and high-pressure cooking to provide food with enhanced organoleptic properties. This work investigates the impact of the cooking process at different pressures on the molecular and sensory profile of a vegetable broth. Experimental results showed similar sensory and chemical profiles of vegetable broths when boiling at 0.93 and 1.5 bar, while an enhancement of sulfur volatile compounds correlated with a greater leek content and savory aroma was observed when boiling at low pressure (80 °C/0.48 bar). Thus, low-pressure cooking would allow preserving the most labile volatiles likely due to the lower water boiling temperature and the reduced level of oxygen. This study evidenced chemical and sensory impact of pressure during cooking and demonstrated that the flavor profile of culinary preparations can be enhanced by applying low-pressure conditions.

Biotechnology and genetic engineering in the new drug development. Part III. Biocatalysis, metabolic engineering and molecular modelling.

PubMed

Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

2013-01-01

Industrial biotechnology has been defined as the use and application of biotechnology for the sustainable processing and production of chemicals, materials and fuels. It makes use of biocatalysts such as microbial communities, whole-cell microorganisms or purified enzymes. In the review these processes are described. Drug design is an iterative process which begins when a chemist identifies a compound that displays an interesting biological profile and ends when both the activity profile and the chemical synthesis of the new chemical entity are optimized. Traditional approaches to drug discovery rely on a stepwise synthesis and screening program for large numbers of compounds to optimize activity profiles. Over the past ten to twenty years, scientists have used computer models of new chemical entities to help define activity profiles, geometries and relativities. This article introduces inter alia the concepts of molecular modelling and contains references for further reading.

Student understanding of pH: "i don't know what the log actually is, i only know where the button is on my calculator".

PubMed

Watters, Dianne J; Watters, James J

2006-07-01

In foundation biochemistry and biological chemistry courses, a major problem area that has been identified is students' lack of understanding of pH, acids, bases, and buffers and their inability to apply their knowledge in solving acid/base problems. The aim of this study was to explore students' conceptions of pH and their ability to solve problems associated with the behavior of biological acids to understand the source of student difficulties. The responses given by most students are characteristic of an atomistic approach in which they pay no attention to the structure of the problem and concentrate only on juggling the elements together until they get a solution. Many students reported difficulty in understanding what the question was asking and were unable to interpret a simple graph showing the pH activity profile of an enzyme. The most startling finding was the lack of basic understanding of logarithms and the inability of all except one student to perform a simple calculation on logs without a calculator. This deficiency in high school mathematical skills severely hampered their understanding of pH. This study has highlighted a widespread deficiency in basic mathematical skills among first year undergraduates and a fragmented understanding of acids and bases. Implications for the way in which the concepts of pH and buffers are taught are discussed. Copyright © 2006 International Union of Biochemistry and Molecular Biology, Inc.

Antagonistic Basic Helix-Loop-Helix/bZIP Transcription Factors Form Transcriptional Modules That Integrate Light and Reactive Oxygen Species Signaling in Arabidopsis[W

PubMed Central

Chen, Dongqin; Xu, Gang; Tang, Weijiang; Jing, Yanjun; Ji, Qiang; Fei, Zhangjun; Lin, Rongcheng

2013-01-01

The critical developmental switch from heterotrophic to autotrophic growth of plants involves light signaling transduction and the production of reactive oxygen species (ROS). ROS function as signaling molecules that regulate multiple developmental processes, including cell death. However, the relationship between light and ROS signaling remains unclear. Here, we identify transcriptional modules composed of the basic helix-loop-helix and bZIP transcription factors PHYTOCHROME-INTERACTING FACTOR1 (PIF1), PIF3, ELONGATED HYPOCOTYL5 (HY5), and HY5 HOMOLOGY (HYH) that bridge light and ROS signaling to regulate cell death and photooxidative response. We show that pif mutants release more singlet oxygen and exhibit more extensive cell death than the wild type during Arabidopsis thaliana deetiolation. Genome-wide expression profiling indicates that PIF1 represses numerous ROS and stress-related genes. Molecular and biochemical analyses reveal that PIF1/PIF3 and HY5/HYH physically interact and coordinately regulate the expression of five ROS-responsive genes by directly binding to their promoters. Furthermore, PIF1/PIF3 and HY5/HYH function antagonistically during the seedling greening process. In addition, phytochromes, cryptochromes, and CONSTITUTIVE PHOTOMORPHOGENIC1 act upstream to regulate ROS signaling. Together, this study reveals that the PIF1/PIF3-HY5/HYH transcriptional modules mediate crosstalk between light and ROS signaling and sheds light on a new mechanism by which plants adapt to the light environments. PMID:23645630

Molecular Profiling of Glatiramer Acetate Early Treatment Effects in Multiple Sclerosis

PubMed Central

Achiron, Anat; Feldman, Anna; Gurevich, Michael

2009-01-01

Background: Glatiramer acetate (GA, Copaxone®) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only partially understood. Objective: To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC). Methods: Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS. Results: GA induced a specific gene expression molecular signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation. Conclusions: Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as molecular markers of GA activity. PMID:19893201

Molecular weight profiles of proanthocyanidin polymers

Treesearch

Vincent M. Williams; Lawrence J. Porter; Richard W. Hemingway

1983-01-01

The MW profiles of proanthocyanidin polymers (condensed tannins) from 32 samples representing a wide range of plant tissues of many different species have been obtained by gel permeation chromatography of the peracetate derivatives. The tannins vary widely in MW, with M values for the peracetates in the range 1600-5500. The MW profiles vary greatly from those with...

Molecular markers in pediatric neuro-oncology.

PubMed

Ichimura, Koichi; Nishikawa, Ryo; Matsutani, Masao

2012-09-01

Pediatric molecular neuro-oncology is a fast developing field. A multitude of molecular profiling studies in recent years has unveiled a number of genetic abnormalities unique to pediatric brain tumors. It has now become clear that brain tumors that arise in children have distinct pathogenesis and biology, compared with their adult counterparts, even for those with indistinguishable histopathology. Some of the molecular features are so specific to a particular type of tumors, such as the presence of the KIAA1549-BRAF fusion gene for pilocytic astrocytomas or SMARCB1 mutations for atypical teratoid/rhabdoid tumors, that they could practically serve as a diagnostic marker on their own. Expression profiling has resolved the existence of 4 molecular subgroups in medulloblastomas, which positively translated into improved prognostication for the patients. The currently available molecular markers, however, do not cover all tumors even within a single tumor entity. The molecular pathogenesis of a large number of pediatric brain tumors is still unaccounted for, and the hierarchy of tumors is likely to be more complex and intricate than currently acknowledged. One of the main tasks of future molecular analyses in pediatric neuro-oncology, including the ongoing genome sequencing efforts, is to elucidate the biological basis of those orphan tumors. The ultimate goal of molecular diagnostics is to accurately predict the clinical and biological behavior of any tumor by means of their molecular characteristics, which is hoped to eventually pave the way for individualized treatment.

Density profiles of granular gases studied by molecular dynamics and Brownian bridges

NASA Astrophysics Data System (ADS)

Peñuñuri, F.; Montoya, J. A.; Carvente, O.

2018-02-01

Despite the inherent frictional forces and dissipative collisions, confined granular matter can be regarded as a system in a stationary state if we inject energy continuously. Under these conditions, both the density and the granular temperature are, in general, non-monotonic variables along the height of the container. In consequence, an analytical description of a granular system is hard to conceive. Here, by using molecular dynamics simulations, we measure the packing fraction profiles for a vertically vibrating three-dimensional granular system in several gaseous-like stationary states. We show that by using the Brownian bridge concept, the determined packing fraction profiles can be reproduced accurately and give a complete description of the distribution of the particles inside the simulation box.

Molecular profiling of the developing avian telencephalon: regional timing and brain subdivision continuities.

PubMed

Chen, Chun-Chun; Winkler, Candace M; Pfenning, Andreas R; Jarvis, Erich D

2013-11-01

In our companion study (Jarvis et al. [2013] J Comp Neurol. doi: 10.1002/cne.23404) we used quantitative brain molecular profiling to discover that distinct subdivisions in the avian pallium above and below the ventricle and the associated mesopallium lamina have similar molecular profiles, leading to a hypothesis that they may form as continuous subdivisions around the lateral ventricle. To explore this hypothesis, here we profiled the expression of 16 genes at eight developmental stages. The genes included those that define brain subdivisions in the adult and some that are also involved in brain development. We found that phyletic hierarchical cluster and linear regression network analyses of gene expression profiles implicated single and mixed ancestry of these brain regions at early embryonic stages. Most gene expression-defined pallial subdivisions began as one ventral or dorsal domain that later formed specific folds around the lateral ventricle. Subsequently a clear ventricle boundary formed, partitioning them into dorsal and ventral pallial subdivisions surrounding the mesopallium lamina. These subdivisions each included two parts of the mesopallium, the nidopallium and hyperpallium, and the arcopallium and hippocampus, respectively. Each subdivision expression profile had a different temporal order of appearance, similar in timing to the order of analogous cell types of the mammalian cortex. Furthermore, like the mammalian pallium, expression in the ventral pallial subdivisions became distinct during prehatch development, whereas the dorsal portions did so during posthatch development. These findings support the continuum hypothesis of avian brain subdivision development around the ventricle and influence hypotheses on homologies of the avian pallium with other vertebrates. Copyright © 2013 Wiley Periodicals, Inc.

Molecular profiling of permafrost soil organic carbon composition and degradation

NASA Astrophysics Data System (ADS)

Gu, B.; Mann, B.

2014-12-01

Microbial degradation of soil organic matter (SOM) is a key process for terrestrial carbon (C) cycling, though the dynamics of these transformations remain unclear at the molecular level. This study reports the application of ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to profile molecular components of Arctic SOM collected from the surface water and the mineral horizon of a low-centered polygon soil at Barrow Environmental Observatory (BEO), Barrow, Alaska. Soil samples were subjected to anaerobic warming experiments for a period of 40 days, and the SOM was extracted before and after the incubation to determine the components of organic C that were degraded over the course of the study. A CHO index based on molecular composition data was utilized to codify SOM components according to their observed degradation potential. Carbohydrate- and lignin-like compounds in the water-soluble fraction (WSF) demonstrated a high degradation potential, while structures with similar stoichiometries in the base-soluble fraction (BSF) were not readily degraded. The WSF of SOM also shifted to a wider range of measured molecular masses including an increased prevalence of larger compounds, while the size distribution of compounds in the BSF changed little over the same period. Additionally, the molecular profiling data indicated an apparently ordered incorporation of organic nitrogen in the BSF immobilized as primary and secondary amines, possibly as components of N-heterocycles, which may provide insight into nitrogen immobilization or mobilization processes in SOM. Our study represents an important step forward for studying Arctic SOM with improved understanding of the molecular properties of soil organic C and the ability to represent SOM in climate models that will predict the impact of climate change on soil C and nutrient cycling.

Prioritization of anti-malarial hits from nature: chemo-informatic profiling of natural products with in vitro antiplasmodial activities and currently registered anti-malarial drugs.

PubMed

Egieyeh, Samuel Ayodele; Syce, James; Malan, Sarel F; Christoffels, Alan

2016-01-29

A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). Natural products with in vitro antiplasmodial activities (NAA) were compiled from various sources. These natural products were sub-divided into four groups based on inhibitory concentration (IC50). Key molecular descriptors and physicochemical properties were computed for these compounds and analysis of variance used to assess statistical significance amongst the sets of compounds. Molecular similarity analysis, estimation of drug-likeness, in silico pharmacokinetic profiling, and exploration of structure-activity landscape were also carried out on these sets of compounds. A total of 1040 natural products were selected and a total of 13 molecular descriptors were analysed. Significant differences were observed among the sub-groups of NAA and CRAD for at least 11 of the molecular descriptors, including number of hydrogen bond donors and acceptors, molecular weight, polar and hydrophobic surface areas, chiral centres, oxygen and nitrogen atoms, and shape index. The remaining molecular descriptors, including clogP, number of rotatable bonds and number of aromatic rings, did not show any significant difference when comparing the two compound sets. Molecular similarity and chemical space analysis identified natural products that were structurally diverse from CRAD. Prediction of the pharmacokinetic properties and drug-likeness of these natural products identified over 50% with desirable drug-like properties. Nearly 70% of all natural products were identified as potentially promiscuous compounds. Structure-activity landscape analysis highlighted compound pairs that form 'activity cliffs'. In all, prioritization strategies for the NAA were proposed. Chemo-informatic profiling of NAA and CRAD have produced a wealth of information that may guide decisions and facilitate anti-malarial drug development from natural products. Articulation of the information provided within an interactive data-mining environment led to a prioritized list of NAA.

The Structural, Functional, and Molecular Organization of the Brainstem

PubMed Central

Nieuwenhuys, Rudolf

2011-01-01

According to His (1891, 1893) the brainstem consists of two longitudinal zones, the dorsal alar plate (sensory in nature) and the ventral basal plate (motor in nature). Johnston and Herrick indicated that both plates can be subdivided into separate somatic and visceral zones, distinguishing somatosensory and viscerosensory zones within the alar plate, and visceromotor and somatomotor zones within the basal plate. To test the validity of this “four-functional-zones” concept, I developed a topological procedure, surveying the spatial relationships of the various cell masses in the brainstem in a single figure. Brainstems of 16 different anamniote species were analyzed, and revealed that the brainstems are clearly divisible into four morphological zones, which correspond largely with the functional zones of Johnston and Herrick. Exceptions include (1) the magnocellular vestibular nucleus situated in the viscerosensory zone; (2) the basal plate containing a number of evidently non-motor centers (superior and inferior olives). Nevertheless the “functional zonal model” has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioral profiles, as “local hypertrophies” of one or two functional columns. Recent developmental molecular studies on brains of birds and mammals confirmed the presence of longitudinal zones, and also showed molecularly defined transverse bands or neuromeres throughout development. The intersecting boundaries of the longitudinal zones and the transverse bands appeared to delimit radially arranged histogenetic domains. Because neuromeres have been observed in embryonic and larval stages of numerous anamniote species, it may be hypothesized that the brainstems of all vertebrates share a basic organizational plan, in which intersecting longitudinal and transverse zones form fundamental histogenetic and genoarchitectonic units. PMID:21738499

Epithelial ovarian cancer: the molecular genetics of epithelial ovarian cancer.

PubMed

Krzystyniak, J; Ceppi, L; Dizon, D S; Birrer, M J

2016-04-01

Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide, despite gains in diagnostics and treatments made over the last three decades. Existing markers of ovarian cancer possess very limited clinical relevance highlighting the emerging need for identification of novel prognostic biomarkers as well as better predictive factors that might allow the stratification of patients who could benefit from a more targeted approach. A summary of molecular genetics of EOC. Large-scale high-throughput genomic technologies appear to be powerful tools for investigations into the genetic abnormalities in ovarian tumors, including studies on dysregulated genes and aberrantly activated signaling pathways. Such technologies can complement well-established clinical histopathology analysis and tumor grading and will hope to result in better, more tailored treatments in the future. Genomic signatures obtained by gene expression profiling of EOC may be able to predict survival outcomes and other important clinical outcomes, such as the success of surgical treatment. Finally, genomic analyses may allow for the identification of novel predictive biomarkers for purposes of treatment planning. These data combined suggest a pathway to progress in the treatment of advanced ovarian cancer and the promise of fulfilling the objective of providing personalized medicine to women with ovarian cancer. The understanding of basic molecular events in the tumorigenesis and chemoresistance of EOC together with discovery of potential biomarkers may be greatly enhanced through large-scale genomic studies. In order to maximize the impact of these technologies, however, extensive validation studies are required. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Welcome to Molecular Brain

PubMed Central

Mei, Lin; Cho, Kei; Lee, C Justin; Li, Xiao-Jiang; Zhuo, Min; Kaang, Bong-Kiun

2008-01-01

We are delighted to announce the arrival of a brand new journal dedicated to the ever-expanding field of neuroscience. Molecular Brain is a peer-reviewed, open-access online journal that aims at publishing high quality articles as rapidly as possible. The journal will cover a broad spectrum of neuroscience ranging from molecular/cellular to behavioral/cognitive neuroscience and from basic to clinical research. Molecular Brain will publish not only research articles, but also methodology articles, editorials, reviews, and short reports. It will be a premier platform for neuroscientists to exchange their ideas with researchers from around the world to help improve our understanding of the molecular mechanisms of the brain and mind. PMID:18803854

Positron Emission Tomography Molecular Imaging in Late-Life Depression

PubMed Central

Hirao, Kentaro; Smith, Gwenn S.

2017-01-01

Molecular imaging represents a bridge between basic and clinical neuroscience observations and provides many opportunities for translation and identifying mechanisms that may inform prevention and intervention strategies in late-life depression (LLD). Substantial advances in instrumentation and radiotracer chemistry have resulted in improved sensitivity and spatial resolution and the ability to study in vivo an increasing number of neurotransmitters, neuromodulators, and, importantly, neuropathological processes. Molecular brain imaging studies in LLD will be reviewed, with a primary focus on positron emission tomography. Future directions for the field of molecular imaging in LLD will be discussed, including integrating molecular imaging with genetic, neuropsychiatric, and cognitive outcomes and multimodality neuroimaging. PMID:24394152

Random Amplified Polymorphic DNA PCR in the Teaching of Molecular Epidemiology

ERIC Educational Resources Information Center

Reinoso, Elina B.; Bettera, Susana G.

2016-01-01

In this article, we describe a basic practical laboratory designed for fifth-year undergraduate students of Microbiology as part of the Epidemiology course. This practice provides the students with the tools for molecular epidemiological analysis of pathogenic microorganisms using a rapid and simple PCR technique. The aim of this work was to assay…

The Fragile X Syndrome: From Molecular Genetics to Neurobiology

ERIC Educational Resources Information Center

Willemsen, Rob; Oostra, Ben A.; Bassell, Gary J.; Dictenberg, Jason

2004-01-01

Since the identification of the FMR1 gene basic research has been focused on the molecular characterization of the FMR1 gene product, the fragile X mental retardation protein (FMRP). Recent developments in fragile X research have provided new insights and knowledge about the physiological function of FMRP in the cell and the nerve cell in…

Th1/Th2 Cytokines: An Easy Model to Study Gene Expression in Immune Cells

ERIC Educational Resources Information Center

Moran, Jose M.; Gonzalez-Polo, Rosa A.; Soler, German; Fuentes, Jose M.

2006-01-01

This report describes a laboratory exercise that was incorporated into a Cell Biology and Molecular Biology advanced course. The exercise was made for a class size with eight students and was designed to reinforce the understanding of basic molecular biology techniques. Students used the techniques of reverse transcription and arginase activity…

Optimal molecular profiling of tissue and tissue components: defining the best processing and microdissection methods for biomedical applications.

PubMed

Bova, G Steven; Eltoum, Isam A; Kiernan, John A; Siegal, Gene P; Frost, Andra R; Best, Carolyn J M; Gillespie, John W; Su, Gloria H; Emmert-Buck, Michael R

2005-02-01

Isolation of well-preserved pure cell populations is a prerequisite for sound studies of the molecular basis of any tissue-based biological phenomenon. This article reviews current methods for obtaining anatomically specific signals from molecules isolated from tissues, a basic requirement for productive linking of phenotype and genotype. The quality of samples isolated from tissue and used for molecular analysis is often glossed over or omitted from publications, making interpretation and replication of data difficult or impossible. Fortunately, recently developed techniques allow life scientists to better document and control the quality of samples used for a given assay, creating a foundation for improvement in this area. Tissue processing for molecular studies usually involves some or all of the following steps: tissue collection, gross dissection/identification, fixation, processing/embedding, storage/archiving, sectioning, staining, microdissection/annotation, and pure analyte labeling/identification and quantification. We provide a detailed comparison of some current tissue microdissection technologies, and provide detailed example protocols for tissue component handling upstream and downstream from microdissection. We also discuss some of the physical and chemical issues related to optimal tissue processing, and include methods specific to cytology specimens. We encourage each laboratory to use these as a starting point for optimization of their overall process of moving from collected tissue to high quality, appropriately anatomically tagged scientific results. In optimized protocols is a source of inefficiency in current life science research. Improvement in this area will significantly increase life science quality and productivity. The article is divided into introduction, materials, protocols, and notes sections. Because many protocols are covered in each of these sections, information relating to a single protocol is not contiguous. To get the greatest benefit from this article, readers are advised to read through the entire article first, identify protocols appropriate to their laboratory for each step in their workflow, and then reread entries in each section pertaining to each of these single protocols.

Optimal molecular profiling of tissue and tissue components: defining the best processing and microdissection methods for biomedical applications.

PubMed

Rodriguez-Canales, Jaime; Hanson, Jeffrey C; Hipp, Jason D; Balis, Ulysses J; Tangrea, Michael A; Emmert-Buck, Michael R; Bova, G Steven

2013-01-01

Isolation of well-preserved pure cell populations is a prerequisite for sound studies of the molecular basis of any tissue-based biological phenomenon. This updated chapter reviews current methods for obtaining anatomically specific signals from molecules isolated from tissues, a basic requirement for productive linking of phenotype and genotype. The quality of samples isolated from tissue and used for molecular analysis is often glossed over or omitted from publications, making interpretation and replication of data difficult or impossible. Fortunately, recently developed techniques allow life scientists to better document and control the quality of samples used for a given assay, creating a foundation for improvement in this area. Tissue processing for molecular studies usually involves some or all of the following steps: tissue collection, gross dissection/identification, fixation, processing/embedding, storage/archiving, sectioning, staining, microdissection/annotation, and pure analyte labeling/identification and quantification. We provide a detailed comparison of some current tissue microdissection technologies and provide detailed example protocols for tissue component handling upstream and downstream from microdissection. We also discuss some of the physical and chemical issues related to optimal tissue processing and include methods specific to cytology specimens. We encourage each laboratory to use these as a starting point for optimization of their overall process of moving from collected tissue to high-quality, appropriately anatomically tagged scientific results. Improvement in this area will significantly increase life science quality and productivity. The chapter is divided into introduction, materials, protocols, and notes subheadings. Because many protocols are covered in each of these sections, information relating to a single protocol is not contiguous. To get the greatest benefit from this chapter, readers are advised to read through the entire chapter first, identify protocols appropriate to their laboratory for each step in their workflow, and then reread entries in each section pertaining to each of these single protocols.

Effect of molecular weight profile of sorghum proanthocyanidins on resistant starch formation.

PubMed

Barros, Frederico; Awika, Joseph; Rooney, Lloyd W

2014-04-01

There is a growing interest to increase resistant starch (RS) in foods through natural modification of starch. Sorghum tannins (proanthocyanidins, PAs) were recently reported to interact with starch, increasing RS. However, there is no information about how the molecular weight profile of PAs affects RS formation. This study investigated how different-molecular-weight PAs from sorghum affected RS formation in different starch models. The levels of RS were higher (331-437 mg g(-1)) when high-amylose starch was cooked with phenolic extracts containing mostly high-molecular-weight PAs compared with extracts containing lower-molecular-weight PAs or monomeric catechin (249-285 mg g(-1)). In general, binding capacity of PAs with amylose increased proportionally with molecular weight. For example, the percentage of PAs bound to amylose increased from 45% (PAs with degree of polymerization (DP) = 6) to 94% (polymeric PAs, DP > 10). The results demonstrate that molecular weight of the PAs directly affects their interaction with starch: the higher the molecular weight, the stronger the binding to amylose and the higher the RS formation. Polymeric PAs from sorghum can naturally modify starch by interacting strongly with amylose and are thus most suitable to produce foods with higher RS. © 2013 Society of Chemical Industry.

Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine.

PubMed

Eke, Iris; Makinde, Adeola Y; Aryankalayil, Molykutty J; Ahmed, Mansoor M; Coleman, C Norman

2016-11-01

New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. Published by Elsevier Ireland Ltd.

Molecular Modeling of Ammonium, Calcium, Sulfur, and Sodium Lignosulphonates in Acid and Basic Aqueous Environments

NASA Astrophysics Data System (ADS)

Salazar Valencia, P. J.; Bolívar Marinez, L. E.; Pérez Merchancano, S. T.

2015-12-01

Lignosulphonates (LS), also known as lignin sulfonates or sulfite lignin, are lignins in sulfonated forms, obtained from the "sulfite liquors," a residue of the wood pulp extraction process. Their main utility lies in its wide range of properties, they can be used as additives, dispersants, binders, fluxing, binder agents, etc. in fields ranging from food to fertilizer manufacture and even as agents in the preparation of ion exchange membranes. Since they can be manufactured relatively easy and quickly, and that its molecular size can be manipulated to obtain fragments of very low molecular weight, they are used as transport agents in the food industry, cosmetics, pharmaceutical and drug development, and as molecular elements for the treatment of health problems. In this paper, we study the electronic structural and optical characteristics of LS incorporating ammonium, sulfur, calcium, and sodium ions in acidic and basic aqueous media in order to gain a better understanding of their behavior and the very interesting properties exhibit. The studies were performed using the molecular modeling program HyperChem 5 using the semiempirical method PM3 of the NDO Family (neglect of differential overlap), to calculate the structural properties. We calculated the electronic and optical properties using the semiempirical method ZINDO / CI.

Quantitative study of mammalian cells by scanning transmission soft X-ray microscopy

NASA Astrophysics Data System (ADS)

Shinohara, K.; Ohigashi, T.; Toné, S.; Kado, M.; Ito, A.

2017-06-01

Molecular distribution in mammalian cells was studied by soft X-ray scanning transmission microscopy with respect to the quantitative aspect of analysis. NEXAFS profiles at the C, N and O K-absorption edges were combined and used for the analysis. For the estimation of quantity for nucleic acids and proteins, NEXAFS profiles of DNA and bovine serum albumin (BSA) at the N K-absorption edge were applied assuming that those were their representatives. The method has a potential to explore the other molecular components than nucleic acids and proteins.

On the probability distribution function of the mass surface density of molecular clouds. II.

NASA Astrophysics Data System (ADS)

Fischera, Jörg

2014-11-01

The probability distribution function (PDF) of the mass surface density of molecular clouds provides essential information about the structure of molecular cloud gas and condensed structures out of which stars may form. In general, the PDF shows two basic components: a broad distribution around the maximum with resemblance to a log-normal function, and a tail at high mass surface densities attributed to turbulence and self-gravity. In a previous paper, the PDF of condensed structures has been analyzed and an analytical formula presented based on a truncated radial density profile, ρ(r) = ρc/ (1 + (r/r0)2)n/ 2 with central density ρc and inner radius r0, widely used in astrophysics as a generalization of physical density profiles. In this paper, the results are applied to analyze the PDF of self-gravitating, isothermal, pressurized, spherical (Bonnor-Ebert spheres) and cylindrical condensed structures with emphasis on the dependence of the PDF on the external pressure pext and on the overpressure q-1 = pc/pext, where pc is the central pressure. Apart from individual clouds, we also consider ensembles of spheres or cylinders, where effects caused by a variation of pressure ratio, a distribution of condensed cores within a turbulent gas, and (in case of cylinders) a distribution of inclination angles on the mean PDF are analyzed. The probability distribution of pressure ratios q-1 is assumed to be given by P(q-1) ∝ q-k1/ (1 + (q0/q)γ)(k1 + k2) /γ, where k1, γ, k2, and q0 are fixed parameters. The PDF of individual spheres with overpressures below ~100 is well represented by the PDF of a sphere with an analytical density profile with n = 3. At higher pressure ratios, the PDF at mass surface densities Σ ≪ Σ(0), where Σ(0) is the central mass surface density, asymptotically approaches the PDF of a sphere with n = 2. Consequently, the power-law asymptote at mass surface densities above the peak steepens from Psph(Σ) ∝ Σ-2 to Psph(Σ) ∝ Σ-3. The corresponding asymptote of the PDF of cylinders for the large q-1 is approximately given by Pcyl(Σ) ∝ Σ-4/3(1 - (Σ/Σ(0))2/3)-1/2. The distribution of overpressures q-1 produces a power-law asymptote at high mass surface densities given by ∝ Σ-2k2 - 1 (spheres) or ∝ Σ-2k2 (cylinders). Appendices are available in electronic form at http://www.aanda.org

Basic Residues of β-Sheet A Contribute to Heparin Binding and Activation of Vaspin (Serpin A12).

PubMed

Ulbricht, David; Oertwig, Kathrin; Arnsburg, Kristin; Saalbach, Anja; Pippel, Jan; Sträter, Norbert; Heiker, John T

2017-01-20

Many members of the serine protease inhibitor (serpin) family are activated by glycosaminoglycans (GAGs). Visceral adipose tissue-derived serpin (vaspin), serpin A12 of the serpin family, and its target protease kallikrein 7 (KLK7) are heparin-binding proteins, and inhibition of KLK7 by vaspin is accelerated by heparin. However, the nature of GAG binding to vaspin is not known. Here, we measured vaspin binding of various glycosaminoglycans and low molecular weight heparins by microscale thermophoresis and analyzed acceleration of protease inhibition by these molecules. In addition, basic residues contributing to heparin binding and heparin activation were identified by a selective labeling approach. Together, these data show that vaspin binds heparin with high affinity (K D = 21 ± 2 nm) and that binding takes place at a basic patch on top of β-sheet A and is different from other heparin-binding serpins. Mutation of basic residues decreased heparin binding and activation of vaspin. Similarly, reactive center loop insertion into sheet A decreased heparin binding because it disturbs the basic cluster. Finally, using vaspin-overexpressing keratinocyte cells, we show that a significant part of secreted vaspin is bound in the extracellular matrix on the cell surface. Together, basic residues of central β-sheet A contribute to heparin binding and activation of vaspin. Thus, binding to GAGs in the extracellular matrix can direct and regulate vaspin interaction with target proteases or other proteins and may play an important role in the various beneficial functions of vaspin in different tissues. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Psychological need satisfaction and well-being in adults aged 80 years and older living in residential homes: using a self-determination theory perspective.

PubMed

Ferrand, Claude; Martinent, Guillaume; Durmaz, Neriman

2014-08-01

Based on the self-determination theory (SDT), this study aims to examine the psychological needs satisfaction of the elderly living in residential homes and their relationship with indicators of well-being, and then to test the contribution of each need on these indicators. Participants (N=100; Mage=86.7 years, SD=3.78) completed the measures of psychological needs satisfaction, purpose in life, personal growth and geriatric depression. Cluster analyses showed two distinct profiles: one profile with a high satisfaction of the three basic psychological needs and another profile with a low satisfaction of the three basic psychological needs. These profiles did not differ in terms of residents' characteristics, health problems and functional limitations. Multivariate analysis of variance (MANOVA) results revealed that the participants with the profile of a high satisfaction of psychological needs have significantly higher levels of purpose in life and personal growth than participants with the profile of a low satisfaction of psychological needs, and no effect of cluster membership on depressive feelings was reported. Moreover, for all participants, relatedness need satisfaction was significantly and positively related to personal growth, and autonomy and relatedness needs satisfaction was related to purpose of life. In conclusion, our results offer evidence that old age can be fruitful and, in consistent with SDT, show that autonomy and relatedness need satisfaction is positively associated with indicators of well-being such as purpose in life and personal growth, considered as essential components of optimal functioning. Copyright © 2014 Elsevier Inc. All rights reserved.

A statistical framework for applying RNA profiling to chemical hazard detection

EPA Science Inventory

Use of ‘omics technologies in environmental science is expanding. However, application is mostly restricted to characterizing molecular steps leading from toxicant interaction with molecular receptors to apical endpoints in laboratory species. Use in environmental decision-...

PCR-Restriction Fragment Length Polymorphism Analysis of the Phospholipase B (PLB1) Gene for Subtyping of Cryptococcus neoformans Isolates

PubMed Central

Latouche, G. Nicolas; Huynh, Matthew; Sorrell, Tania C.; Meyer, Wieland

2003-01-01

Cryptococcus neoformans is a pathogenic yeast that is currently divided into three varieties, five serotypes, and eight molecular types. The following report describes the use of PCR-restriction fragment length polymorphism (RFLP) analysis of the phospholipase B gene (PLB1) as a simple tool to differentiate between C. neoformans subgroups. A PLB1 fragment, 1,970 bp, was amplified and digested with either AvaI or HindIII. Both sets of profiles grouped the isolates into their respective varieties, but only the AvaI profiles allowed for the identification of the eight molecular types via the corresponding RFLP profiles A1 to A8. Digestion of the same fragments with HindIII resulted in RFLP profiles H1 to H5, which distinguished only between serotype A, AD, D, and B/C. Neither enzyme distinguished serotype B from serotype C. The serotype AD profile was a composite of the serotype A and D profiles. Further investigation showed that the serotype AD isolates used in this study are heterozygous, with one allele of PLB1 originating from a serotype A parent and the other from a serotype D parent. PMID:12676686

Specialized project in biophotonics

NASA Astrophysics Data System (ADS)

Garcia Martin, Agueda L.; Sastriques-Silva, Pedro O.; Martinez-Fundora, Julia N.; Augier Calderin, Angel G.; Lopez-Cepero, Xonia

2000-06-01

As science advances, it is more evident the necessity of a health interdisciplinary approach in Medicine. In the case of medical applications of light, the knowledge of the use of dispositives, equipment, diagnostic and treatment means, as well as the bases for the use of this update technologies is required. At the present moment, the outstanding work of specialized professionals of different profiles requires personnel with high professional formation in keeping with the latest trends in science and technology. The authors present here an Specialized Project in Biophotonics, with the aim of increasing the professional preparation of university graduates with an ample profile--physicists and engineers--who work in Biomedical Optics, thus contributing to the specialized formation of medic and paramedic personnel. The course is structured into six-subject-modules and into two phases. As to the basic professional formation, each one attending this course, will select between two variants of the Basic Formation Postgraduate Course: Anatomy and Physiology, Physical Bioenergetics, Clinic Bioenergetics; or Physics in Medicine, Optics and Applied Information Theory, depending on the student's professional profile. In the second phase, the General Formation Postgraduate Course: Biomedical Optics, Optical Bioenergetics and Laser in Medicine.

Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Large-Scale Epidemiology: A Primer on -Omic Technologies

PubMed Central

Kangas, Antti J; Soininen, Pasi; Lawlor, Debbie A; Davey Smith, George; Ala-Korpela, Mika

2017-01-01

Abstract Detailed metabolic profiling in large-scale epidemiologic studies has uncovered novel biomarkers for cardiometabolic diseases and clarified the molecular associations of established risk factors. A quantitative metabolomics platform based on nuclear magnetic resonance spectroscopy has found widespread use, already profiling over 400,000 blood samples. Over 200 metabolic measures are quantified per sample; in addition to many biomarkers routinely used in epidemiology, the method simultaneously provides fine-grained lipoprotein subclass profiling and quantification of circulating fatty acids, amino acids, gluconeogenesis-related metabolites, and many other molecules from multiple metabolic pathways. Here we focus on applications of magnetic resonance metabolomics for quantifying circulating biomarkers in large-scale epidemiology. We highlight the molecular characterization of risk factors, use of Mendelian randomization, and the key issues of study design and analyses of metabolic profiling for epidemiology. We also detail how integration of metabolic profiling data with genetics can enhance drug development. We discuss why quantitative metabolic profiling is becoming widespread in epidemiology and biobanking. Although large-scale applications of metabolic profiling are still novel, it seems likely that comprehensive biomarker data will contribute to etiologic understanding of various diseases and abilities to predict disease risks, with the potential to translate into multiple clinical settings. PMID:29106475

Identification of Potential Chemical Carcinogens in Compendia of Gene Expression Profiles

EPA Science Inventory

Chemicals induce cancer through partially characterized adverse outcome pathways (AOPs) that include molecular initiating events (MIEs) and downstream key events (KEs). Microarray profiling of chemical-induced effects is being increasingly used in medium- and high-throughput form...

An Easily Constructed and Versatile Molecular Model

NASA Astrophysics Data System (ADS)

Hernandez, Sandra A.; Rodriguez, Nora M.; Quinzani, Oscar

1996-08-01

Three-dimensional molecular models are powerful tools used in basic courses of general and organic chemistry when the students must visualize the spatial distributions of atoms in molecules and relate them to the physical and chemical properties of such molecules. This article discusses inexpensive, easily carried, and semipermanent molecular models that the students may build by themselves. These models are based upon two different types of arrays of thin flexible wires, like telephone hook-up wires, which may be bent easily but keep their shapes.

Molecular Mechanisms of Neuroplasticity: An Expanding Universe.

PubMed

Gulyaeva, N V

2017-03-01

Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.

Pathology of the human pituitary adenomas

PubMed Central

Kajiya, Hanako; Takei, Mao; Egashira, Noboru; Tobita, Maya; Takekoshi, Susumu; Teramoto, Akira

2008-01-01

This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology. PMID:18688636

Molecular profiling of marine fauna: integration of omics with environmental assessment of the world's oceans.

PubMed

Veldhoen, Nik; Ikonomou, Michael G; Helbing, Caren C

2012-02-01

Many species that contribute to the commercial and ecological richness of our marine ecosystems are harbingers of environmental change. The ability of organisms to rapidly detect and respond to changes in the surrounding environment represents the foundation for application of molecular profiling technologies towards marine sentinel species in an attempt to identify signature profiles that may reside within the transcriptome, proteome, or metabolome and that are indicative of a particular environmental exposure event. The current review highlights recent examples of the biological information obtained for marine sentinel teleosts, mammals, and invertebrates. While in its infancy, such basal information can provide a systems biology framework in the detection and evaluation of environmental chemical contaminant effects on marine fauna. Repeated evaluation across different seasons and local marine environs will lead to discrimination between signature profiles representing normal variation within the complex milieu of environmental factors that trigger biological response in a given sentinel species and permit a greater understanding of normal versus anthropogenic-associated modulation of biological pathways, which prove detrimental to marine fauna. It is anticipated that incorporation of contaminant-specific molecular signatures into current risk assessment paradigms will lead to enhanced wildlife management strategies that minimize the impacts of our industrialized society on marine ecosystems. Copyright © 2011 Elsevier Inc. All rights reserved.

Integrated genomic classification of melanocytic tumors of the central nervous system using mutation analysis, copy number alterations and DNA methylation profiling.

PubMed

Griewank, Klaus; Koelsche, Christian; van de Nes, Johannes A P; Schrimpf, Daniel; Gessi, Marco; Möller, Inga; Sucker, Antje; Scolyer, Richard A; Buckland, Michael E; Murali, Rajmohan; Pietsch, Torsten; von Deimling, Andreas; Schadendorf, Dirk

2018-06-11

In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria can be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis. Targeted next-generation-sequencing, array-based genome-wide methylation analysis and BAP1 immunohistochemistry was performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, incl. 47 primary tumors of the central nervous system, 16 uveal melanomas. 13 cutaneous melanoma metastasis and 2 blue nevus-like melanomas. Gene mutation, DNA-methylation and copy-number profiles were correlated with clinicopathological features. Combining mutation, copy-number and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas and blue nevus-like melanoma showed common DNA-methylation, copy-number alteration and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group. Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma and blue nevus-like melanoma share molecular similarity with chromosome 3 and BAP1 alterations markers of poor prognosis. Copyright ©2018, American Association for Cancer Research.

The circadian clock of Neurospora crassa.

PubMed

Baker, Christopher L; Loros, Jennifer J; Dunlap, Jay C

2012-01-01

Circadian clocks organize our inner physiology with respect to the external world, providing life with the ability to anticipate and thereby better prepare for major fluctuations in its environment. Circadian systems are widely represented in nearly all major branches of life, except archaebacteria, and within the eukaryotes, the filamentous fungus Neurospora crassa has served for nearly half a century as a durable model organism for uncovering the basic circadian physiology and molecular biology. Studies using Neurospora have clarified our fundamental understanding of the clock as nested positive and negative feedback loops regulated through transcriptional and post-transcriptional processes. These feedback loops are centered on a limited number of proteins that form molecular complexes, and their regulation provides a physical explanation for nearly all clock properties. This review will introduce the basics of circadian rhythms, the model filamentous fungus N. crassa, and provide an overview of the molecular components and regulation of the circadian clock. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

ACOG Technology Assessment No. 11: Genetics and molecular diagnostic testing.

PubMed

2014-02-01

Human genetics and molecular testing are playing an increasingly important role in medicine, including obstetric and gynecologic practice. As the genetic basis for reproductive disorders, common diseases, and cancer is elucidated with improved molecular technology, genetic testing opportunities are expanding and influencing treatment options and prevention strategies. It is essential that obstetrician-gynecologists be aware of advances in the understanding of genetic disease and the fundamental principles of genetic screening and molecular testing as genetics becomes a more integral part of routine medical practice. This document reviews the basics of genetic transmission and genetic technologies in current use.

Characterizations of structural, biochemical, and nutritive profiles in silage among cool-season corn cultivars in relation to heat units (aCHU, dCHU) with curvilinear response and multivariate analyses.

PubMed

Abeysekara, Saman; Christensen, David A; Yu, Peiqiang

2013-12-18

Molecular spectroscopy is able to reveal structural features of biomaterials. Corn grown in Canadian prairies is known as cool-season corn, which is different from warm-season corn varieties. To our knowledge, to date, there has been no study on the magnitude difference in structure on a molecular basis among cultivars, no study on biochemical and nutritive profiles associated with heat unit, and no study on how heat unit affects the molecular structure and biochemical and nutritive profiles. This study investigates how corn varieties grown in cooler climates are affected by crop heat units (CHU) in relation to molecular spectral profiles, nutrient storage, biochemical composition, and nutritive value of silage among different cool-season corn cultivars. Corn cultivars (Pioneer and Dekalb) were from seven farm locations, and samples were analyzed for major nutrients (digestible and metabolic energy and protein). The Fourier transform infrared (FT/IR) spectroscopic technique was applied to understand and differentiate molecular structural spectral profiles in silage. A correlation (P < 0.05) of CHU with some nutrients (mean ± SD, %DM) (CP, 8.1 ± 1.3, r = 0.56; NDF, 56.3 ± 3.5, r = -0.54; ADF, 33.6 ± 2.3, r = -0.71; NDICP, 1.6 ± 0.4, r = -0.66; SCP, 4.2 ± 1.3, r = 0.61), protein and carbohydrate fractions (mean ± SD, %DM) (PB1 (= fast degradable protein fraction), 1.3 ± 0.4, r = 0.54; PB3 (= slowly degradable protein fraction), 1.5 ± 0.4, r = -0.74; CB2 (= medium degradable carbohydrate fraction), 45.1 ± 2.8, r = -0.65; CB3 (= slowly degradable carbohydrate fraction), 13.9 ± 0.9, r = -0.54) and intestinal availability of ruminally degraded fractions (mean ± SD, %DM) (rdPB1, 1.1 ± 0.3, r = 0.54; rdPB3, 1.0 ± 0.3, r = -0.74; RDP, 6.6 ± 1.2, r = 0.59; rdCB2, 40.0 ± 2.5, r = -0.65; rdCB3, 8.9 ± 0.6, r = 0.54; RDCHO, 50.1 ± 2.9, r = -0.65) was found contentious. Molecular spectral data indicated many similarities and few differences among the cultivars. However, CHU correlated (r = -0.4, P < 0.05) with molecular spectral intensity ratio of carbohydrate to amide I. This result indicates that molecular structural differences may be influenced by epiphytic bacterial compounds. Cool corn cultivars were grown acceptably well in cooler dry climates, and those silages had acceptable nutrient levels for cattle. Cultivars that reached target CHU were found to be optimal in nutrient and energy synchronization aspect.

On the reduction of occultation light curves. [stellar occultations by planets

NASA Technical Reports Server (NTRS)

Wasserman, L.; Veverka, J.

1973-01-01

The two basic methods of reducing occultation light curves - curve fitting and inversion - are reviewed and compared. It is shown that the curve fitting methods have severe problems of nonuniqueness. In addition, in the case of occultation curves dominated by spikes, it is not clear that such solutions are meaningful. The inversion method does not suffer from these drawbacks. Methods of deriving temperature profiles from refractivity profiles are then examined. It is shown that, although the temperature profiles are sensitive to small errors in the refractivity profile, accurate temperatures can be obtained, particularly at the deeper levels of the atmosphere. The ambiguities that arise when the occultation curve straddles the turbopause are briefly discussed.

Optimizing parameters of GTU cycle and design values of air-gas channel in a gas turbine with cooled nozzle and rotor blades

NASA Astrophysics Data System (ADS)

Kler, A. M.; Zakharov, Yu. B.

2012-09-01

The authors have formulated the problem of joint optimization of pressure and temperature of combustion products before gas turbine, profiles of nozzle and rotor blades of gas turbine, and cooling air flow rates through nozzle and rotor blades. The article offers an original approach to optimization of profiles of gas turbine blades where the optimized profiles are presented as linear combinations of preliminarily formed basic profiles. The given examples relate to optimization of the gas turbine unit on the criterion of power efficiency at preliminary heat removal from air flows supplied for the air-gas channel cooling and without such removal.

Molecular profile of tumor-specific CD8+ T cell hypofunction in a transplantable murine cancer model1

PubMed Central

Waugh, Katherine A.; Leach, Sonia M.; Moore, Brandon L.; Bruno, Tullia C.; Buhrman, Jonathan D.; Slansky, Jill E.

2016-01-01

Mechanisms of self-tolerance often result in CD8+ tumor-infiltrating lymphocytes (TIL) with a hypofunctional phenotype incapable of tumor clearance. Using a transplantable colon carcinoma model, we found that CD8+ T cells became tolerized in less than 24 hours in an established tumor environment. To define the collective impact of pathways suppressing TIL function, we compared genome-wide mRNA expression of tumor-specific CD8+ T cells from the tumor and periphery. Notably, gene expression induced during TIL hypofunction more closely resembled self-tolerance than viral-exhaustion. Differential gene expression was refined to identify a core set of genes that defined hypofunctional TIL; these data comprise the first “molecular profile” of tumor-specific TIL that are naturally responding and represent a polyclonal repertoire. The molecular profile of TIL was further dissected to determine the extent of overlap and distinction between pathways that collectively restrict T cell functions. As suggested by the molecular profile of TIL, protein expression of inhibitory receptor LAG-3 was differentially regulated throughout prolonged late-G1/early-S phase of the cell cycle. Our data may accelerate efficient identification of combination therapies to boost anti-tumor function of TIL specifically against tumor cells. PMID:27371726

On the Origin of Water Flow through Carbon Nanotubes.

PubMed

Su, Jiaye; Yang, Keda

2015-11-16

The transport of water molecules through carbon nanotubes (CNTs) is of primary importance for understanding water-mediated biological activities as well as for the design of novel nanoporous materials. Herein, we analyze the water flow through CNTs by using molecular dynamics simulations with the hope of finding basic parameters determining the flow value. Of particular interest is that a simple equation as a function of water diffusion, occupancy and CNT size, can well describe the water flow through CNTs with different sizes. Specifically, both the simulation and equation flow exhibit power law relations with the CNT diameter and length, where the two exponents are close to each other. The water occupancy and translocation time also demonstrate interesting relations with the CNT size. The water dipole orientations and density profiles are also sensitive to the change of CNT size. These results greatly enhance our knowledge on the nature of water flow through CNTs and are helpful in predicting the water flow of CNTs up to the experimental length scale. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Hybrid Methacrylate-Sodium Carboxymethylcellulose Interpolyelectrolyte Complex: Rheometry and in Silico Disposition for Controlled Drug Release

PubMed Central

Ngwuluka, Ndidi Chinyelu; Choonara, Yahya Essop; Kumar, Pradeep; Modi, Girish; du Toit, Lisa Claire; Pillay, Viness

2013-01-01

The rheological behavioral changes that occurred during the synthesis of an interpolyelectrolyte complex (IPEC) of methacrylate copolymer and sodium carboxymethylcellulose were assessed. These changes were compared with the rheological behavior of the individual polymers employing basic viscosity, yield stress, stress sweep, frequency sweep, temperature ramp as well as creep and recovery testing. The rheological studies demonstrated that the end-product of the complexation of low viscous methacrylate copolymer and entangled solution of sodium carboxymethylcellulose generated a polymer, which exhibited a solid-like behavior with a three-dimensional network. Additionally, the rheological profile of the sodium carboxymethylcellulose and methacrylate copolymer with respect to the effect of various concentrations of acetic acid on the synthesis of the IPEC was elucidated using molecular mechanics energy relationships (MMER) by exploring the spatial disposition of carboxymethylcellulose and methacrylate copolymer with respect to each other and acetic acid. The computational results corroborated well with the experimental in vitro drug release data. Results have shown that the IPEC may be suitable polymeric material for achieving controlled zero-order drug delivery. PMID:28788332

Label-Free Optofluidic Nanobiosensor Enables Real-Time Analysis of Single-Cell Cytokine Secretion.

PubMed

Li, Xiaokang; Soler, Maria; Szydzik, Crispin; Khoshmanesh, Khashayar; Schmidt, Julien; Coukos, George; Mitchell, Arnan; Altug, Hatice

2018-06-01

Single-cell analysis of cytokine secretion is essential to understand the heterogeneity of cellular functionalities and develop novel therapies for multiple diseases. Unraveling the dynamic secretion process at single-cell resolution reveals the real-time functional status of individual cells. Fluorescent and colorimetric-based methodologies require tedious molecular labeling that brings inevitable interferences with cell integrity and compromises the temporal resolution. An innovative label-free optofluidic nanoplasmonic biosensor is introduced for single-cell analysis in real time. The nanobiosensor incorporates a novel design of a multifunctional microfluidic system with small volume microchamber and regulation channels for reliable monitoring of cytokine secretion from individual cells for hours. Different interleukin-2 secretion profiles are detected and distinguished from single lymphoma cells. The sensor configuration combined with optical spectroscopic imaging further allows us to determine the spatial single-cell secretion fingerprints in real time. This new biosensor system is anticipated to be a powerful tool to characterize single-cell signaling for basic and clinical research. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bartonella: emerging pathogen or emerging awareness?

PubMed

Mogollon-Pasapera, Elin; Otvos, Laszlo; Giordano, Antonio; Cassone, Marco

2009-01-01

The number of known Bartonella species is rapidly growing. Some of them are responsible for distinct infectious diseases and show different prevalence and antibiotic susceptibility profiles. Not only have some vectors of Bartonella not been fully characterized, but also intermediate hosts are actually much more numerous and diverse than previously thought. Among these, dogs differ from cats because they tend to suffer an overt disease similar to humans, thus providing the base for a useful animal indicator and research model. Among the debilitating conditions with an unclear impact on the course of these infections, specific conditions (e.g., homelessness, alcoholism) have been linked to a much higher prevalence and to high risk of unfavorable outcome. Due to the limited arsenal of antibiotics effective in vivo on this peculiar intracellular pathogen, the risk/benefit balance of antibiotic therapy is sometimes difficult to draw. In this evolving picture, the recent discoveries of new species highlights the importance of basic molecular biology resources that would bring major public health benefits if available in endemic areas, and specifically in many areas of Peru and Bolivia.

The detailed chemistry and thermodynamics of sodium in oxygen-rich flames

NASA Technical Reports Server (NTRS)

Hynes, A. J.; Steinberg, M.; Schofield, K.

1982-01-01

Measurement of sodium and OH concentrations in ten oxygen-rich H2/O2/N2 flames by respective saturated and low-power laser induced fluorescence techniques have permitted a detailed examination of the pronounced flame chemistry of sodium in such oxygen rich media. Previous interpretations have been shown to be largely incomplete or in error. The flame downstream profiles indicate that the amount of free sodium tracks the decay of H-atom and as the flame radicals decay sodium becomes increasingly bound in a molecular form. A detailed kinetic model indicates that the sodium is distributed between NaOH and NaO2 species. Concentrations of NaO are very small and NaH negligible. The actual distribution is controlled by the state of equilibrium of the flames' basic free radicals. Na, NaO2 and NaOH are all coupled to one another by fast reactions which can rapidly interconvert one to another as flame conditions vary. Above about 2000K, NaOH becomes dominant whereas NaO2 plays an increasingly important contribution at lower temperatures.

The research infrastructure of Chinese foundations, a database for Chinese civil society studies

PubMed Central

Ma, Ji; Wang, Qun; Dong, Chao; Li, Huafang

2017-01-01

This paper provides technical details and user guidance on the Research Infrastructure of Chinese Foundations (RICF), a database of Chinese foundations, civil society, and social development in general. The structure of the RICF is deliberately designed and normalized according to the Three Normal Forms. The database schema consists of three major themes: foundations’ basic organizational profile (i.e., basic profile, board member, supervisor, staff, and related party tables), program information (i.e., program information, major program, program relationship, and major recipient tables), and financial information (i.e., financial position, financial activities, cash flow, activity overview, and large donation tables). The RICF’s data quality can be measured by four criteria: data source reputation and credibility, completeness, accuracy, and timeliness. Data records are properly versioned, allowing verification and replication for research purposes. PMID:28742065

Basic research for development of the beam profile monitor based on a Faraday cup array system

NASA Astrophysics Data System (ADS)

Park, Mook-Kwang

2015-10-01

The basic design used to develop a beam profile monitor based on a Faraday cup array (FCA), which has the advantages of high robustness, reliability, and long-term stability, along with the ability to measure the ion current over a wide dynamic range, was developed. The total system is divided into three parts: i.e., a faraday cup, measuring electronics, and a display program part. The FCA was considered to consist of a collimator, suppressor, insulator frame, and 64 (8 × 8 array) tiny Faraday cups (FC). An electronic circuit using a multiplexer was applied to effectively address many signal lines and the printed circuit board (PCB) was designed to be divided into three parts, i.e., an electrode PCB (ELEC PCB), capacitance PCB (CAP PCB), and control PCB (CON PCB).

Comprehensive and quantitative profiling of lipid species in human milk, cow milk and a phospholipid-enriched milk formula by GC and MS/MSALL.

PubMed

Sokol, Elena; Ulven, Trond; Færgeman, Nils J; Ejsing, Christer S

2015-06-01

Here we present a workflow for in-depth analysis of milk lipids that combines gas chromatography (GC) for fatty acid (FA) profiling and a shotgun lipidomics routine termed MS/MS ALL for structural characterization of molecular lipid species. To evaluate the performance of the workflow we performed a comparative lipid analysis of human milk, cow milk, and Lacprodan® PL-20, a phospholipid-enriched milk protein concentrate for infant formula. The GC analysis showed that human milk and Lacprodan have a similar FA profile with higher levels of unsaturated FAs as compared to cow milk. In-depth lipidomic analysis by MS/MS ALL revealed that each type of milk sample comprised distinct composition of molecular lipid species. Lipid class composition showed that the human and cow milk contain a higher proportion of triacylglycerols (TAGs) as compared to Lacprodan. Notably, the MS/MS ALL analysis demonstrated that the similar FA profile of human milk and Lacprodan determined by GC analysis is attributed to the composition of individual TAG species in human milk and glycerophospholipid species in Lacprodan. Moreover, the analysis of TAG molecules in Lacprodan and cow milk showed a high proportion of short-chain FAs that could not be monitored by GC analysis. The results presented here show that complementary GC and MS/MS ALL analysis is a powerful approach for characterization of molecular lipid species in milk and milk products. : Milk lipid analysis is routinely performed using gas chromatography. This method reports the total fatty acid composition of all milk lipids, but provides no structural or quantitative information about individual lipid molecules in milk or milk products. Here we present a workflow that integrates gas chromatography for fatty acid profiling and a shotgun lipidomics routine termed MS/MS ALL for structural analysis and quantification of molecular lipid species. We demonstrate the efficacy of this complementary workflow by a comparative analysis of molecular lipid species in human milk, cow milk, and a milk-based supplement used for infant formula.

Comprehensive and quantitative profiling of lipid species in human milk, cow milk and a phospholipid-enriched milk formula by GC and MS/MSALL

PubMed Central

Sokol, Elena; Ulven, Trond; Færgeman, Nils J; Ejsing, Christer S

2015-01-01

Here we present a workflow for in-depth analysis of milk lipids that combines gas chromatography (GC) for fatty acid (FA) profiling and a shotgun lipidomics routine termed MS/MSALL for structural characterization of molecular lipid species. To evaluate the performance of the workflow we performed a comparative lipid analysis of human milk, cow milk, and Lacprodan® PL-20, a phospholipid-enriched milk protein concentrate for infant formula. The GC analysis showed that human milk and Lacprodan have a similar FA profile with higher levels of unsaturated FAs as compared to cow milk. In-depth lipidomic analysis by MS/MSALL revealed that each type of milk sample comprised distinct composition of molecular lipid species. Lipid class composition showed that the human and cow milk contain a higher proportion of triacylglycerols (TAGs) as compared to Lacprodan. Notably, the MS/MSALL analysis demonstrated that the similar FA profile of human milk and Lacprodan determined by GC analysis is attributed to the composition of individual TAG species in human milk and glycerophospholipid species in Lacprodan. Moreover, the analysis of TAG molecules in Lacprodan and cow milk showed a high proportion of short-chain FAs that could not be monitored by GC analysis. The results presented here show that complementary GC and MS/MSALL analysis is a powerful approach for characterization of molecular lipid species in milk and milk products. Practical applications : Milk lipid analysis is routinely performed using gas chromatography. This method reports the total fatty acid composition of all milk lipids, but provides no structural or quantitative information about individual lipid molecules in milk or milk products. Here we present a workflow that integrates gas chromatography for fatty acid profiling and a shotgun lipidomics routine termed MS/MSALL for structural analysis and quantification of molecular lipid species. We demonstrate the efficacy of this complementary workflow by a comparative analysis of molecular lipid species in human milk, cow milk, and a milk-based supplement used for infant formula. PMID:26089741

Molecular characterization and expression profiles of four transformer-2 isoforms in the Chinese mitten crab Eriocheir sinensis

NASA Astrophysics Data System (ADS)

Luo, Danli; Liu, Yuan; Hui, Min; Song, Chengwen; Liu, Hourong; Cui, Zhaoxia

2017-07-01

The transformer-2 ( tra-2) gene plays a key role in the regulatory hierarchy of sexual differentiation in somatic tissues and in the germline of Drosophila melanogaster. In this study, sequences and expression profiles of tra-2 in the Chinese mitten crab Eriocheir sinensis were characterized. Four tra-2 isoforms, designated as Estra-2a, Estra-2b, Estra-2c, and Estra-2d, were isolated. They all contained an RNA-recognition motif (RRM) and a linker region, which shared high similarity with other reported tra-2s. Sequence analysis revealed that Estra-2a, Estra-2b and Estra-2c are encoded by the same genomic locus and are generated by alternative splicing of the pre-mRNA. Compared with the other three isoforms, Estra-2d lacks the RS2 domain. Quantitative real-time PCR showed that all four isoforms were highly expressed in the fertilized egg, and in the 2-4 cell and blastula stages compared with larval stages ( P≤0.01), suggesting their maternal origin in early embryonic developmental stages. Notably, Estra-2a was highly expressed in male somatic tissues, while Estra-2c was significantly highly expressed in the ovary. These results suggest that Estra-2c is involved in sexual differentiation of the Chinese mitten crab. Our findings provide basic information for further functional studies of the tra-2 gene/protein in this species.

Instability of Hydrogenated TiO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nandasiri, Manjula I.; Shutthanandan, V.; Manandhar, Sandeep

2015-11-06

Hydrogenated TiO2 (H-TiO2) is toted as a viable visible light photocatalyst. We report a systematic study on the thermal stability of H-implanted TiO2 using X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), Rutherford backscattering spectrometry (RBS) and nuclear reaction analysis (NRA). Protons (40 keV) implanted at a ~2 atom % level within a ~120 nm wide profile of rutile TiO2(110) were situated ~300 nm below the surface. NRA revealed that this H-profile broadened preferentially toward the surface after annealing at 373 K, dissipated out of the crystal into vacuum at 473 K, and was absent within the beam sampling depthmore » (~800 nm) at 523 K. Photoemission showed that the surface was reduced in concert with these changes. Similar anneals had no effect on pristine TiO2(110). The facile bulk diffusivity of H in rutile, as well as its activity toward interfacial reduction, significantly limits the utilization of H-TiO2 as a photocatalyst. This work was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. The research was performed using the Environmental Molecular Sciences Laboratory (EMSL), a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory.« less

Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique.

PubMed

Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

2017-04-26

In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed.

Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique

PubMed Central

Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

2017-01-01

In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed. PMID:28445393

Introducing Basic Molecular Biology to Turkish Rural and Urban Primary School Children via Hands-on PCR and Gel Electrophoresis Activities

ERIC Educational Resources Information Center

Selli, Cigdem; Yildirim, Gokce; Kaymak, Aysegul; Karacicek, Bilge; Ogut, Deniz; Gungor, Turkan; Erem, Erdem; Ege, Mehmet; Bümen, Nilay; Tosun, Metiner

2014-01-01

This study includes the results of a 2-day education project titled "Molecular Biology Laboratory Summer School, MoBiLYO." The project was held at a University Research Center by scientists from Department of Pharmacology and graduate students. The project was composed of introductory lectures, model construction, DNA isolation,…

77 FR 56855 - Center For Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-14

... Review Group; Molecular Genetics A Study Section. Date: October 15-16, 2012. Time: 8:00 a.m. to 6:00 p.m... Genetics Study Section. Date: October 15, 2012. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and evaluate...: Oncology 1--Basic Translational Integrated Review Group; Cancer Molecular Pathobiology Study Section. Date...

Molecular Biology Masterclasses--Developing Practical Skills and Building Links with Higher Education in Years 12/13

ERIC Educational Resources Information Center

Hooley, Paul; Cooper, Phillippa; Skidmore, Nick

2008-01-01

A one day practical course in molecular biology skills suitable for year 12/13 students is described. Colleagues from partner schools and colleges were trained by university staff in basic techniques and then collaborated in the design of a course suitable for their own students. Participants carried out a transformation of "E.coli"…

Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins.

PubMed

Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

2016-03-05

The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm(-1) and 1545 cm(-1), respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties. Copyright © 2015 Elsevier B.V. All rights reserved.

GENE-07. MOLECULAR NEUROPATHOLOGY 2.0 - INCREASING DIAGNOSTIC ACCURACY IN PEDIATRIC NEUROONCOLOGY

PubMed Central

Sturm, Dominik; Jones, David T.W.; Capper, David; Sahm, Felix; von Deimling, Andreas; Rutkoswki, Stefan; Warmuth-Metz, Monika; Bison, Brigitte; Gessi, Marco; Pietsch, Torsten; Pfister, Stefan M.

2017-01-01

Abstract The classification of central nervous system (CNS) tumors into clinically and biologically distinct entities and subgroups is challenging. Children and adolescents can be affected by >100 histological variants with very variable outcomes, some of which are exceedingly rare. The current WHO classification has introduced a number of novel molecular markers to aid routine neuropathological diagnostics, and DNA methylation profiling is emerging as a powerful tool to distinguish CNS tumor classes. The Molecular Neuropathology 2.0 study aims to integrate genome wide (epi-)genetic diagnostics with reference neuropathological assessment for all newly-diagnosed pediatric brain tumors in Germany. To date, >350 patients have been enrolled. A molecular diagnosis is established by epigenetic tumor classification through DNA methylation profiling and targeted panel sequencing of >130 genes to detect diagnostically and/or therapeutically useful DNA mutations, structural alterations, and fusion events. Results are aligned with the reference neuropathological diagnosis, and discrepant findings are discussed in a multi-disciplinary tumor board including reference neuroradiological evaluation. Ten FFPE sections as input material are sufficient to establish a molecular diagnosis in >95% of tumors. Alignment with reference pathology results in four broad categories: a) concordant classification (~77%), b) discrepant classification resolvable by tumor board discussion and/or additional data (~5%), c) discrepant classification without currently available options to resolve (~8%), and d) cases currently unclassifiable by molecular diagnostics (~10%). Discrepancies are enriched in certain histopathological entities, such as histological high grade gliomas with a molecularly low grade profile. Gene panel sequencing reveals predisposing germline events in ~10% of patients. Genome wide (epi-)genetic analyses add a valuable layer of information to routine neuropathological diagnostics. Our study provides insight into CNS tumors with divergent histopathological and molecular classification, opening new avenues for research discoveries and facilitating optimization of clinical management for affected patients in the future.

Molecular profiling in Italian patients with advanced non-small-cell lung cancer: An observational prospective study.

PubMed

Gobbini, Elisa; Galetta, Domenico; Tiseo, Marcello; Graziano, Paolo; Rossi, Antonio; Bria, Emilio; Di Maio, Massimo; Rossi, Giulio; Gregorc, Vanesa; Riccardi, Ferdinando; Scotti, Vieri; Ceribelli, Anna; Buffoni, Lucio; Delmonte, Angelo; Franchina, Tindara; Migliorino, Maria Rita; Cortinovis, Diego; Pisconti, Salvatore; Bordi, Paola; Catino, Annamaria; Maiello, Evaristo; Arizio, Francesca; Novello, Silvia

2017-09-01

Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015. Information regarding molecular profiling and treatment choices were collected. Description of patients' outcome included overall survival (OS), progression-free survival in first (PFS1) and second-line (PFS2). Among 1787 patients enrolled, 1388 (78%) performed at least one molecular analysis during the history of disease: 76% were tested for EGFR, 53% for ALK, 27% for KRAS, 16% for ROS1, 14% for BRAF, 5% for HER2, 4% for MET and 1% for FGFR. The remaining 399 patients (22.3%) did not receive any molecular test. Among patients receiving at least one molecular analysis, 583 (42%) presented a molecular alteration. Considering EGFR mutated and/or ALK rearranged patients (402), for which target agents were routinely reimbursed at time of study in Italy, the 86% received a personalized treatment as first and/or second line: the 90% (286) of EGFR mutants received an EGFR tyrosine kinase inhibitor, mostly gefitinib (41.1%) or afatinib (36.4%) while 74% (62) of ALK translocated patients received an ALK inhibitor, mostly crizotinib (64%). Median OS was 9.34 months (95% CI 8.62-10.0), median PFS1 was 4.61 months (95%CI 4.31-4.84) and median PFS2 was 2.76 months (95%CI 2.57-3.19). In the Italian clinical practice, routine molecular assessment was largely applied in NSCLC patients, according to national guidelines, but a low level of ALK test was reached. Most of EGFR mutants an ALK rearranged patients received a personalized treatment as first and/or second line. Copyright © 2017 Elsevier B.V. All rights reserved.

A molecular quantum spin network controlled by a single qubit.

PubMed

Schlipf, Lukas; Oeckinghaus, Thomas; Xu, Kebiao; Dasari, Durga Bhaktavatsala Rao; Zappe, Andrea; de Oliveira, Felipe Fávaro; Kern, Bastian; Azarkh, Mykhailo; Drescher, Malte; Ternes, Markus; Kern, Klaus; Wrachtrup, Jörg; Finkler, Amit

2017-08-01

Scalable quantum technologies require an unprecedented combination of precision and complexity for designing stable structures of well-controllable quantum systems on the nanoscale. It is a challenging task to find a suitable elementary building block, of which a quantum network can be comprised in a scalable way. We present the working principle of such a basic unit, engineered using molecular chemistry, whose collective control and readout are executed using a nitrogen vacancy (NV) center in diamond. The basic unit we investigate is a synthetic polyproline with electron spins localized on attached molecular side groups separated by a few nanometers. We demonstrate the collective readout and coherent manipulation of very few (≤ 6) of these S = 1/2 electronic spin systems and access their direct dipolar coupling tensor. Our results show that it is feasible to use spin-labeled peptides as a resource for a molecular qubit-based network, while at the same time providing simple optical readout of single quantum states through NV magnetometry. This work lays the foundation for building arbitrary quantum networks using well-established chemistry methods, which has many applications ranging from mapping distances in single molecules to quantum information processing.

Probing the Reproducibility of Leaf Growth and Molecular Phenotypes: A Comparison of Three Arabidopsis Accessions Cultivated in Ten Laboratories1[W

PubMed Central

Massonnet, Catherine; Vile, Denis; Fabre, Juliette; Hannah, Matthew A.; Caldana, Camila; Lisec, Jan; Beemster, Gerrit T.S.; Meyer, Rhonda C.; Messerli, Gaëlle; Gronlund, Jesper T.; Perkovic, Josip; Wigmore, Emma; May, Sean; Bevan, Michael W.; Meyer, Christian; Rubio-Díaz, Silvia; Weigel, Detlef; Micol, José Luis; Buchanan-Wollaston, Vicky; Fiorani, Fabio; Walsh, Sean; Rinn, Bernd; Gruissem, Wilhelm; Hilson, Pierre; Hennig, Lars; Willmitzer, Lothar; Granier, Christine

2010-01-01

A major goal of the life sciences is to understand how molecular processes control phenotypes. Because understanding biological systems relies on the work of multiple laboratories, biologists implicitly assume that organisms with the same genotype will display similar phenotypes when grown in comparable conditions. We investigated to what extent this holds true for leaf growth variables and metabolite and transcriptome profiles of three Arabidopsis (Arabidopsis thaliana) genotypes grown in 10 laboratories using a standardized and detailed protocol. A core group of four laboratories generated similar leaf growth phenotypes, demonstrating that standardization is possible. But some laboratories presented significant differences in some leaf growth variables, sometimes changing the genotype ranking. Metabolite profiles derived from the same leaf displayed a strong genotype × environment (laboratory) component. Genotypes could be separated on the basis of their metabolic signature, but only when the analysis was limited to samples derived from one laboratory. Transcriptome data revealed considerable plant-to-plant variation, but the standardization ensured that interlaboratory variation was not considerably larger than intralaboratory variation. The different impacts of the standardization on phenotypes and molecular profiles could result from differences of temporal scale between processes involved at these organizational levels. Our findings underscore the challenge of describing, monitoring, and precisely controlling environmental conditions but also demonstrate that dedicated efforts can result in reproducible data across multiple laboratories. Finally, our comparative analysis revealed that small variations in growing conditions (light quality principally) and handling of plants can account for significant differences in phenotypes and molecular profiles obtained in independent laboratories. PMID:20200072

Transcriptome profiling analysis of cultivar-specific apple fruit ripening and texture attributes

USDA-ARS?s Scientific Manuscript database

Molecular events regulating cultivar-specific apple fruit ripening and sensory quality are largely unknown. Such knowledge is essential for genomic-assisted apple breeding and postharvest quality management. In this study, transcriptome profile analysis, scanning electron microscopic examination an...

Attitude profile design program

NASA Technical Reports Server (NTRS)

1991-01-01

The Attitude Profile Design (APD) Program was designed to be used as a stand-alone addition to the Simplex Computation of Optimum Orbital Trajectories (SCOOT). The program uses information from a SCOOT output file and the user defined attitude profile to produce time histories of attitude, angular body rates, and accelerations. The APD program is written in standard FORTRAN77 and should be portable to any machine that has an appropriate compiler. The input and output are through formatted files. The program reads the basic flight data, such as the states of the vehicles, acceleration profiles, and burn information, from the SCOOT output file. The user inputs information about the desired attitude profile during coasts in a high level manner. The program then takes these high level commands and executes the maneuvers, outputting the desired information.

Correlating molecular spectroscopy and molecular chemometrics to explore carbohydrate functional groups and utilization of coproducts from biofuel and biobrewing processing.

PubMed

Chen, Limei; Zhang, Xuewei; Yu, Peiqiang

2014-06-04

Dried distillers grains with solubles (DDGS) was coproducts from bioethanol and biobrewing industry. It was an excellent resource of protein and energy feedstuff in China. Conventional studies often focus on traditional nutritional profiles. To data, there is little research on molecular structure-nutrition interaction of carbohydrate in coproducts. In this study, five kinds of corn-grain based DDGS and two kinds of barley-grain based DDGS were collected from different manufactures in the north of China. They were coded as "1, 2, 3, 4, 5, 6, and 7", respectively. The primary purposes of this project were to investigate the molecular structure-nutrition interaction of carbohydrate in coproducts, in terms of (1) carbohydrate-related chemical composition and nutrient profiles, (2) predicted values for energy in coproducts for animal, and (3) in situ digestion of dry matter. The result showed that acid detergent fiber content in corn DDGS and barley DDGS had negative correlation with structural carbohydrate peak area, cellulose compounds, and carbohydrate component peaks (first, second, and total peak area), which were measured with molecular spectroscopy. The correlation between carbohydrate peak area (second and total) and digestible fiber (tdNDF) were negative. There were no correlation between carbohydrate spectral intensities and energy values, carbohydrate subfractions partitioned by CNCPS system, and in situ rumen degradation. The results indicate that carbohydrate spectral profiles (functional groups) are associated with the carbohydrate nutritive values in coproducts from biofuel and biobrewing processing.

Gas kinematics in the H II regions G351.69-1.15 and G351.63-1.25

NASA Astrophysics Data System (ADS)

Veena, V. S.; Vig, S.; Tej, A.; Kantharia, N. G.; Ghosh, S. K.

2017-03-01

We probe the structure and kinematics of two neighbouring H II regions identified as cometary and bipolar, using radio recombination lines (RRLs). The H172α RRLs from these H II regions: G351.69-1.15 and G351.63-1.25, are mapped using Giant Metrewave Radio Telescope, India. We also detect carbon RRLs C172α towards both these regions. The hydrogen RRLs display the effects of pressure and dynamical broadening in the line profiles, with the dynamical broadening (∼15 km s-1) playing a major role in the observed profile of G351.69-1.15. We investigate the kinematics of molecular gas species towards this H II region from the Millimetre Astronomy Legacy Team 90 GHz Pilot Survey. The molecular gas is mostly distributed towards the north and north-west of the cometary head. The molecular line profiles indicate signatures of turbulence and outflow in this region. The ionized gas at the cometary tail is blueshifted by ∼8 km s-1 with respect to the ambient molecular cloud, consistent with the earlier proposed champagne flow scenario. The relative velocity of ∼5 km s-1 between the northern and southern lobes of the bipolar H II region G351.63-1.25 is consistent with the premise that the bipolar morphology is a result of the expanding ionized lobes within a flat molecular cloud.

A scaling law of radial gas distribution in disk galaxies

NASA Technical Reports Server (NTRS)

Wang, Zhong

1990-01-01

Based on the idea that local conditions within a galactic disk largely determine the region's evolution time scale, researchers built a theoretical model to take into account molecular cloud and star formations in the disk evolution process. Despite some variations that may be caused by spiral arms and central bulge masses, they found that many late-type galaxies show consistency with the model in their radial atomic and molecular gas profiles. In particular, researchers propose that a scaling law be used to generalize the gas distribution characteristics. This scaling law may be useful in helping to understand the observed gas contents in many galaxies. Their model assumes an exponential mass distribution with disk radius. Most of the mass are in atomic gas state at the beginning of the evolution. Molecular clouds form through a modified Schmidt Law which takes into account gravitational instabilities in a possible three-phase structure of diffuse interstellar medium (McKee and Ostriker, 1977; Balbus and Cowie, 1985); whereas star formation proceeds presumably unaffected by the environmental conditions outside of molecular clouds (Young, 1987). In such a model both atomic and molecular gas profiles in a typical galactic disk (as a result of the evolution) can be fitted simultaneously by adjusting the efficiency constants. Galaxies of different sizes and masses, on the other hand, can be compared with the model by simply scaling their characteristic length scales and shifting their radial ranges to match the assumed disk total mass profile sigma tot(r).

Molecular markers in pediatric neuro-oncology

PubMed Central

Ichimura, Koichi; Nishikawa, Ryo; Matsutani, Masao

2012-01-01

Pediatric molecular neuro-oncology is a fast developing field. A multitude of molecular profiling studies in recent years has unveiled a number of genetic abnormalities unique to pediatric brain tumors. It has now become clear that brain tumors that arise in children have distinct pathogenesis and biology, compared with their adult counterparts, even for those with indistinguishable histopathology. Some of the molecular features are so specific to a particular type of tumors, such as the presence of the KIAA1549-BRAF fusion gene for pilocytic astrocytomas or SMARCB1 mutations for atypical teratoid/rhabdoid tumors, that they could practically serve as a diagnostic marker on their own. Expression profiling has resolved the existence of 4 molecular subgroups in medulloblastomas, which positively translated into improved prognostication for the patients. The currently available molecular markers, however, do not cover all tumors even within a single tumor entity. The molecular pathogenesis of a large number of pediatric brain tumors is still unaccounted for, and the hierarchy of tumors is likely to be more complex and intricate than currently acknowledged. One of the main tasks of future molecular analyses in pediatric neuro-oncology, including the ongoing genome sequencing efforts, is to elucidate the biological basis of those orphan tumors. The ultimate goal of molecular diagnostics is to accurately predict the clinical and biological behavior of any tumor by means of their molecular characteristics, which is hoped to eventually pave the way for individualized treatment. PMID:23095836

[The 40th anniversary of RAMS institute of human morphology].

PubMed

Kakturskiĭ, L V; Shakhlamov, V A

2002-01-01

Institute of Human Morphology of Russian Academy of Medical Sciences was established in 1961 and united efforts of morphologists of various profile--pathologists, cytologists, embryologists. The role of outstanding Russian morphologists and the first Institute heads is shown. Basic achievements in four research fields are characterized: in geographic pathology; structural basis of immune homeostasis in health and pathology; pathologic anatomy and pathogenesis of basic human diseases; human morpho- and embriogenesis in health and disease.

Investigation of technical problems related to deployment and retrieval of spinning satellites

NASA Technical Reports Server (NTRS)

Kaplan, M. H.

1973-01-01

Results of a three-year research effort on retrieval and deployment problems associated with orbiting payloads are summarized. Answers to several basic questions about rendezvous, docking, and deployment dynamics and controls were obtained. A basic retrieval mission profile was formulated in order to develop relevant technology. A remotely controlled retrieval package was conceived. Special deployment dynamics problems associated with high altitude deployment were investigated, and new knowledge of payload spin reorientation was obtained.

Improving the developability profile of pyrrolidine progesterone receptor partial agonists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.

2010-09-17

The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

Sorption of carboxylic acid from carboxylic salt solutions at PHS close to or above the pK.sub.a of the acid, with regeneration with an aqueous solution of ammonia or low-molecular-weight alkylamine

DOEpatents

King, C. Judson; Tung, Lisa A.

1992-01-01

Carboxylic acids are sorbed from aqueous feedstocks at pHs close to or above the acids' pH.sub.a into a strongly basic organic liquid phase or onto a basic solid adsorbent or moderately basic ion exchange resin. the acids are freed from the sorbent phase by treating it with aqueous alkylamine or ammonia thus forming an alkylammonium or ammonium carobxylate which dewatered and decomposed to the desired carboxylic acid and the alkylamine or ammonia.

Molecular profiles suggest two types of liver cancer should be treated as one | Center for Cancer Research

Cancer.gov

A comprehensive molecular analysis of two types of liver cancer, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), has identified common molecular subtypes that can be found among patients with either disease. Although HCC and ICC are considered separate diseases, the finding suggests that a unified clinical approach could benefit patients with both

Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review.

PubMed

Borazanci, Erkut; Millis, Sherri Z; Korn, Ron; Han, Haiyong; Whatcott, Clifford J; Gatalica, Zoran; Barrett, Michael T; Cridebring, Derek; Von Hoff, Daniel D

2015-09-15

Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient's tumor. Further work should be pursued to better characterize this disease.

The East German Research Landscape in Transition. Part B. Non-University Institutes

DTIC Science & Technology

1993-03-02

struc- tures and metal ions: Basic research of the biosorption , bioaccumulation and metal desorption mechanisms Influence and increase of the sorption...microbial corrosion problems - Investigation of che interaction between microbial structures and metal ions: Basic research of the biosorption ...Additional work has been undertaken on the response of the cell at the molecular level to various stresses, including heat and heavy metals . In both cases

Environmental microbiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitchell, R.

1992-01-01

This book covers issues ranging from global climate changes to biocontrol of plant diseases. Many of its contributions stress how new technologies in areas such as molecular biology and environmental engineering expand understanding and applications of basic concepts in environmental microbiology. Articles in the book are in three basic subject areas: effects of environmental contamination on the role of microbes in geochemical cycling of the major elements, pathogens in the environment, and microbial activities in environmental management.

Study of the coumarate decarboxylase and vinylphenol reductase activities of Dekkera bruxellensis (anamorph Brettanomyces bruxellensis) isolates.

PubMed

Godoy, L; Garrido, D; Martínez, C; Saavedra, J; Combina, M; Ganga, M A

2009-04-01

To evaluate the coumarate descarboxylase (CD) and vinylphenol reductase (VR) activities in Dekkera bruxellensis isolates and study their relationship to the growth rate, protein profile and random amplified polymorphic DNA (RAPD) molecular pattern. CD and VR activities were quantified, as well, the growth rate, intracellular protein profile and molecular analysis (RAPD) were determined in 12 isolates of D. bruxellensis. All the isolates studied showed CD activity, but only some showed VR activity. Those isolates with the greatest growth rate did not present a different protein profile from the others. The FASC showed a relationship between RAPD molecular patterns and VR activity. CD activity is common to all of the D. bruxellensis isolates. This was not the case with VR activity, which was detected at a low percentage in the analysed micro-organisms. A correlation was observed between VR activity and the RAPD patterns. This is the first study that quantifies the CD and VR enzyme activities in D. bruxellensis, demonstrating that these activities are not present in all isolates of this yeast.

Mitigating the Problem of Unmeasured Outcomes in Quality Reports

PubMed Central

Glazer, Jacob; McGuire, Thomas; Normand, Sharon-Lise T.

2009-01-01

Quality reports or profiles of health care providers are inevitably based on only a measurable subset of the “outputs” of the organization. Hospitals, for example, are being profiled on their mortality in the cardiac area but not in some other areas where mortality does not seem to be the appropriate measure of quality. If inputs used for outputs included in the profile also affect outputs outside the scope of the profile, it can be taken into account in constructing a profile of the measured outputs. This paper presents a theory for how such a commonality in production should be taken into account in designing a profile for a hospital or other health care provider. We distinguish between “conventional” weights in a quality profile, and “optimal” weights that take into account a commonality in the production process. The basic idea is to increase the weights on discharges for which output is measured that use inputs that are important to other discharges whose outputs are not included in the profile. PMID:20490360

Structural Biology and Molecular Applications Research

Cancer.gov

Part of NCI's Division of Cancer Biology's research portfolio, research and development in this area focuses on enabling technologies, models, and methodologies to support basic and applied cancer research.

High Spectral Resolution Lidar Measurements of Multiple Scattering

NASA Technical Reports Server (NTRS)

Eloranta, E. W.; Piironen, P.

1996-01-01

The University of Wisconsin High Spectral Resolution Lidar (HSRL) provides unambiguous measurements of backscatter cross section, backscatter phase function, depolarization, and optical depth. This is accomplished by dividing the lidar return into separate particulate and molecular contributions. The molecular return is then used as a calibration target. We have modified the HSRL to use an I2 molecular absorption filter to separate aerosol and molecular signals. This allows measurement in dense clouds. Useful profiles extend above the cloud base until the two way optical depth reaches values between 5 and 6; beyond this, photon counting errors become large. In order to observe multiple scattering, the HSRL includes a channel which records the combined aerosol and molecular lidar return simultaneously with the spectrometer channel measurements of optical properties. This paper describes HSRL multiple scattering measurements from both water and ice clouds. These include signal strengths and depolarizations as a function of receiver field of view. All observations include profiles of extinction and backscatter cross sections. Measurements are also compared to predictions of a multiple scattering model based on small angle approximations.

Advances in Molecular Pathology and Treatment of Periampullary Cancers.

PubMed

Chandrasegaram, Manju D; Chen, John W; Price, Timothy J; Zalcberg, John; Sjoquist, Katrin; Merrett, Neil D

2016-01-01

Periampullary cancers (PACs) include the following 4 traditional anatomic subtypes: pancreatic, ampullary, biliary, or duodenal cancers. This review was performed to highlight recent advances in the genomic and molecular understanding of each PAC subtype and the advances in chemotherapeutic and molecular trials in these cancer subtypes. Recent advances have highlighted differences in the genomic and molecular features within each PAC subtype. Ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. K-ras mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42%-52%), biliary (22%-23%), and duodenal cancers (32%-35%), suggesting crucial differences in targetable mutations in these cancer subtypes.Ampullary cancers of intestinal subtype and duodenal cancers seem to share similarities with colorectal cancer, given that they respond to similar chemotherapeutic regimens. This has potential implications for clinical trials and treatment selection, where PACs are often considered together. Future trials should be designed in view of our increased understanding of the different anatomic and histomolecularly profiled subtypes of PAC cancers, which respects their individual molecular characteristics, phenotype, and response to treatment.

Study of the photovoltaic effect in thin film barium titanate

NASA Technical Reports Server (NTRS)

Grannemann, W. W.; Dharmadhikari, V. S.

1982-01-01

The basic mechanism associated with the photovoltaic phenomena observed in the R.F. sputtered BaTiO3/silicon system is presented. Series of measurements of short circuit photocurrents and open circuit photovoltage were made. The composition depth profiles and the interface characteristics of the BaTiO3/silicon system were investigated for a better understanding of the electronic properties. A Scanning Auger Microprobe combined with ion in depth profiling were used.

Phenotypic and Molecular Antibiotic Resistance Determination of Airborne Coagulase Negative Staphylococcus spp. Strains from Healthcare Facilities in Southern Poland.

PubMed

Lenart-Boroń, Anna; Wolny-Koładka, Katarzyna; Stec, Joanna; Kasprowic, Andrzej

2016-10-01

This study assessed the antimicrobial resistance of airborne Staphylococcus spp. strains isolated from healthcare facilities in southern Poland. A total of 55 isolates, belonging to 10 coagulase-negative staphylococci (CoNS) species, isolated from 10 healthcare facilities (including hospitals and outpatient units) were included in the analysis. The most frequently identified species were Staphylococcus saprophyticus and Staphylococcus warneri, which belong to normal human skin flora, but can also be the cause of common and even severe nosocomial infections. Disk diffusion tests showed that the bacterial strains were most frequently resistant to erythromycin and tetracycline and only 18% of strains were susceptible to all tested antimicrobials. Polymerase chain reaction amplification of specific gene regions was used to determine the presence of the Macrolide-Lincosamide-Streptogramin resistance mechanisms in CoNS. The molecular analysis, conducted using specific primer pairs, identified the msrA1 gene, encoding active efflux pumps in bacterial cells, as the most frequent resistance gene. As many as seven antibiotic resistance genes were found in one isolate, whereas the most common number of resistance genes per isolate was five (n = 17). It may be concluded that drug resistance was widely spread among the tested strains, but the resulting antimicrobial resistance profile indicates that in the case of infection, the use of antibiotics from the basic antibiogram group will be effective in therapy. However, before administering treatment, determination of the specific antimicrobial resistance should be conducted, particularly in the case of hospitalized patients.

Proteomic analysis during of spore germination of Moniliophthora perniciosa, the causal agent of witches' broom disease in cacao.

PubMed

Mares, Joise Hander; Gramacho, Karina Peres; Santos, Everton Cruz; da Silva Santiago, André; Santana, Juliano Oliveira; de Sousa, Aurizângela Oliveira; Alvim, Fátima Cerqueira; Pirovani, Carlos Priminho

2017-08-17

Moniliophthora perniciosa is a phytopathogenic fungus responsible for witches' broom disease of cacao trees (Theobroma cacao L.). Understanding the molecular events during germination of the pathogen may enable the development of strategies for disease control in these economically important plants. In this study, we determined a comparative proteomic profile of M. perniciosa basidiospores during germination by two-dimensional SDS-PAGE and mass spectrometry. A total of 316 proteins were identified. Molecular changes during the development of the germinative tube were identified by a hierarchical clustering analysis based on the differential accumulation of proteins. Proteins associated with fungal filamentation, such as septin and kinesin, were detected only 4 h after germination (hag). A transcription factor related to biosynthesis of the secondary metabolite fumagillin, which can form hybrids with polyketides, was induced 2 hag, and polyketide synthase was observed 4 hag. The accumulation of ATP synthase, binding immunoglobulin protein (BiP), and catalase was validated by western blotting. In this study, we showed variations in protein expression during the early germination stages of fungus M. perniciosa. Proteins associated with fungal filamentation, and consequently with virulence, were detected in basidiospores 4 hag., for example, septin and kinesin. We discuss these results and propose a model of the germination of fungus M. perniciosa. This research can help elucidate the mechanisms underlying basic processes of host invasion and to develop strategies for control of the disease.

NMR and MS Methods for Metabolomics.

PubMed

Amberg, Alexander; Riefke, Björn; Schlotterbeck, Götz; Ross, Alfred; Senn, Hans; Dieterle, Frank; Keck, Matthias

2017-01-01

Metabolomics, also often referred as "metabolic profiling," is the systematic profiling of metabolites in biofluids or tissues of organisms and their temporal changes. In the last decade, metabolomics has become more and more popular in drug development, molecular medicine, and other biotechnology fields, since it profiles directly the phenotype and changes thereof in contrast to other "-omics" technologies. The increasing popularity of metabolomics has been possible only due to the enormous development in the technology and bioinformatics fields. In particular, the analytical technologies supporting metabolomics, i.e., NMR, UPLC-MS, and GC-MS, have evolved into sensitive and highly reproducible platforms allowing the determination of hundreds of metabolites in parallel. This chapter describes the best practices of metabolomics as seen today. All important steps of metabolic profiling in drug development and molecular medicine are described in great detail, starting from sample preparation to determining the measurement details of all analytical platforms, and finally to discussing the corresponding specific steps of data analysis.

NMR and MS methods for metabonomics.

PubMed

Dieterle, Frank; Riefke, Björn; Schlotterbeck, Götz; Ross, Alfred; Senn, Hans; Amberg, Alexander

2011-01-01

Metabonomics, also often referred to as "metabolomics" or "metabolic profiling," is the systematic profiling of metabolites in bio-fluids or tissues of organisms and their temporal changes. In the last decade, metabonomics has become increasingly popular in drug development, molecular medicine, and other biotechnology fields, since it profiles directly the phenotype and changes thereof in contrast to other "-omics" technologies. The increasing popularity of metabonomics has been possible only due to the enormous development in the technology and bioinformatics fields. In particular, the analytical technologies supporting metabonomics, i.e., NMR, LC-MS, UPLC-MS, and GC-MS have evolved into sensitive and highly reproducible platforms allowing the determination of hundreds of metabolites in parallel. This chapter describes the best practices of metabonomics as seen today. All important steps of metabolic profiling in drug development and molecular medicine are described in great detail, starting from sample preparation, to determining the measurement details of all analytical platforms, and finally, to discussing the corresponding specific steps of data analysis.

Profiling charge complementarity and selectivity for binding at the protein surface.

PubMed

Sulea, Traian; Purisima, Enrico O

2003-05-01

A novel analysis and representation of the protein surface in terms of electrostatic binding complementarity and selectivity is presented. The charge optimization methodology is applied in a probe-based approach that simulates the binding process to the target protein. The molecular surface is color coded according to calculated optimal charge or according to charge selectivity, i.e., the binding cost of deviating from the optimal charge. The optimal charge profile depends on both the protein shape and charge distribution whereas the charge selectivity profile depends only on protein shape. High selectivity is concentrated in well-shaped concave pockets, whereas solvent-exposed convex regions are not charge selective. This suggests the synergy of charge and shape selectivity hot spots toward molecular selection and recognition, as well as the asymmetry of charge selectivity at the binding interface of biomolecular systems. The charge complementarity and selectivity profiles map relevant electrostatic properties in a readily interpretable way and encode information that is quite different from that visualized in the standard electrostatic potential map of unbound proteins.

Molecular profiles of Venezuelan isolates of Trypanosoma sp. by random amplified polymorphic DNA method.

PubMed

Perrone, T M; Gonzatti, M I; Villamizar, G; Escalante, A; Aso, P M

2009-05-12

Nine Trypanosoma sp. Venezuelan isolates, initially presumed to be T. evansi, were collected from three different hosts, capybara (Apure state), horse (Apure state) and donkey (Guarico state) and compared by the random amplification polymorphic DNA technique (RAPD). Thirty-one to 46 reproducible fragments were obtained with 12 of the 40 primers that were used. Most of the primers detected molecular profiles with few polymorphisms between the seven horse, capybara and donkey isolates. Quantitative analyses of the RAPD profiles of these isolates revealed a high degree of genetic conservation with similarity coefficients between 85.7% and 98.5%. Ten of the primers generated polymorphic RAPD profiles with two of the three Trypanosoma sp. horse isolates, namely TeAp-N/D1 and TeGu-N/D1. The similarity coefficient between these two isolates and the rest, ranged from 57.9% to 68.4% and the corresponding dendrogram clustered TeAp-N/D1 and Te Gu-N/D1 in a genetically distinct group.

Existence of Inverted Profile in Chemically Responsive Molecular Pathways in the Zebrafish Liver

PubMed Central

Zhang, Xun; Li, Hu; Ma, Jing; Zhang, Louxin; Li, Baowen; Gong, Zhiyuan

2011-01-01

How a living organism maintains its healthy equilibrium in response to endless exposure of potentially harmful chemicals is an important question in current biology. By transcriptomic analysis of zebrafish livers treated by various chemicals, we defined hubs as molecular pathways that are frequently perturbed by chemicals and have high degree of functional connectivity to other pathways. Our network analysis revealed that these hubs were organized into two groups showing inverted functionality with each other. Intriguingly, the inverted activity profiles in these two groups of hubs were observed to associate only with toxicopathological states but not with physiological changes. Furthermore, these inverted profiles were also present in rat, mouse, and human under certain toxicopathological conditions. Thus, toxicopathological-associated anti-correlated profiles in hubs not only indicate their potential use in diagnosis but also development of systems-based therapeutics to modulate gene expression by chemical approach in order to rewire the deregulated activities of hubs back to normal physiology. PMID:22140468

Characterization of fructans and dietary fibre profiles in raw and steamed vegetables.

PubMed

Kalala, Gaétan; Kambashi, Bienvenu; Everaert, Nadia; Beckers, Yves; Richel, Aurore; Pachikian, Barbara; Neyrinck, Audrey M; Delzenne, Nathalie M; Bindelle, Jérôme

2017-12-18

Dietary fibre (DF) has many positive effects on human health associated with its functionality in the gastrointestinal tract. These benefits vary according to the type of DF. Vegetables can be a natural source of DF in the diet. However, to provide adequate nutritional advice, the content and profile of their various DF types must be characterised. This study aimed to determine the DF profile of 29 vegetables cultivated in Wallonia (Belgium) and the impact of steaming on these profiles. Using a combination of enzymatic, gravimetric and chromatographic methods, fructans, total dietary fibre (TDF), low- and high-molecular-weight soluble dietary fibre (SDF), and insoluble dietary fibre (IDF) were analysed. Results show that the DF content varies considerably among the 29 investigated vegetable varieties and species, but the influence of steaming is limited to a shift from IDF to high-molecular-weight SDF for 18 of the 29 tested vegetables, while fructans are preserved with not actual reduction in the DP.

Disruption of Fibroblast Growth Factor Receptor (FGFR) Signaling as an Approach to Prostate Cancer Therapy

DTIC Science & Technology

2006-04-01

and the abstract was published in the Journal of Molecular Diagnostics . The full length manuscript entitled “Increased expression and activity of...Recurrence. The Journal of Molecular Diagnostics 2004, (6)4: 431. Ozen M, Dixit S and Ittmann M: Molecular profiling of differentially expressed genes...in response to FGFR disruption in prostate cancer. the Journal of Molecular Diagnostics 7 (5): 680, 2005. Full Articles: 1. Ozen M and Ittmann M

Use of mutation profiles to refine the classification of endometrial carcinomas.

PubMed

McConechy, Melissa K; Ding, Jiarui; Cheang, Maggie Cu; Wiegand, Kimberly; Senz, Janine; Tone, Alicia; Yang, Winnie; Prentice, Leah; Tse, Kane; Zeng, Thomas; McDonald, Helen; Schmidt, Amy P; Mutch, David G; McAlpine, Jessica N; Hirst, Martin; Shah, Sohrab P; Lee, Cheng-Han; Goodfellow, Paul J; Gilks, C Blake; Huntsman, David G

2012-09-01

The classification of endometrial carcinomas is based on pathological assessment of tumour cell type; the different cell types (endometrioid, serous, carcinosarcoma, mixed, undifferentiated, and clear cell) are associated with distinct molecular alterations. This current classification system for high-grade subtypes, in particular the distinction between high-grade endometrioid (EEC-3) and serous carcinomas (ESC), is limited in its reproducibility and prognostic abilities. Therefore, a search for specific molecular classifiers to improve endometrial carcinoma subclassification is warranted. We performed target enrichment sequencing on 393 endometrial carcinomas from two large cohorts, sequencing exons from the following nine genes: ARID1A, PPP2R1A, PTEN, PIK3CA, KRAS, CTNNB1, TP53, BRAF, and PPP2R5C. Based on this gene panel, each endometrial carcinoma subtype shows a distinct mutation profile. EEC-3s have significantly different frequencies of PTEN and TP53 mutations when compared to low-grade endometrioid carcinomas. ESCs and EEC-3s are distinct subtypes with significantly different frequencies of mutations in PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1. From the mutation profiles, we were able to identify subtype outliers, ie cases diagnosed morphologically as one subtype but with a mutation profile suggestive of a different subtype. Careful review of these diagnostically challenging cases suggested that the original morphological classification was incorrect in most instances. The molecular profile of carcinosarcomas suggests two distinct mutation profiles for these tumours: endometrioid-type (PTEN, PIK3CA, ARID1A, KRAS mutations) and serous-type (TP53 and PPP2R1A mutations). While this nine-gene panel does not allow for a purely molecularly based classification of endometrial carcinoma, it may prove useful as an adjunct to morphological classification and serve as an aid in the classification of problematic cases. If used in practice, it may lead to improved diagnostic reproducibility and may also serve to stratify patients for targeted therapeutics. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets- An Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

PubMed Central

Ilekis, John V.; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M.; Soares, Michael J.; Cross, James C.; Zamudio, Stacy; Illsley, Nicholas P.; Myatt, Leslie; Colvis, Christine; Costantine, Maged M.; Haas, David M.; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

2016-01-01

Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles of microRNAs and placental-derived exosomes, as well as messenger RNAs, were also discussed in the context of their use for diagnostics and as drug targets. The workshop discussed the aspect of safety and pharmacokinetic profiles of potential existing and new therapeutics that will need to be determined especially in the context of the unique pharmacokinetic properties of pregnancy, as well as the hurdles and pitfalls of translating research findings into practice. The workshop also discussed novel methods of drug delivery and targeting during pregnancy using macromolecular carriers, such as nanoparticles and biopolymers, to minimize placental drug transfer and hence fetal drug exposure. In closing, a major theme that developed from the workshop was that the scientific community needs to change their thinking of the pregnant women and her fetus as a vulnerable patient population for which drug development should be avoided, but rather thought of as a deprived population in need of more effective therapeutic interventions. PMID:26972897

Basic Beaches for the Classroom.

ERIC Educational Resources Information Center

McLaren, J. Philip

1986-01-01

Lists and explains the major characteristics of water. Compares water's molecular structure and its temperature-related properties with four other lightweight molecules. Discusses why water is considered the universal solvent. (ML)

New Genetics

MedlinePlus

... Century-Old Evolutionary Puzzle Computing Genetics Model Organisms RNA Interference The New Genetics is a science education ... the basics of DNA and its molecular cousin RNA, and new directions in genetic research. The New ...

Differential transmission of the molecular signature of RBSP3, LIMD1 and CDC25A in basal/ parabasal versus spinous of normal epithelium during head and neck tumorigenesis: A mechanistic study.

PubMed

Sarkar, Shreya; Alam, Neyaz; Mandal, Syam Sundar; Chatterjee, Kabita; Ghosh, Supratim; Roychoudhury, Susanta; Panda, Chinmay Kumar

2018-01-01

Head and neck squamous cell carcinoma (HNSCC) is a global disease and mortality burden, necessitating the elucidation of its molecular progression for effective disease management. The study aims to understand the molecular profile of three candidate cell cycle regulatory genes, RBSP3, LIMD1 and CDC25A in the basal/ parabasal versus spinous layer of normal oral epithelium and during head and neck tumorigenesis. Immunohistochemical expression and promoter methylation was used to determine the molecular signature in normal oral epithelium. The mechanism of alteration transmission of this profile during tumorigenesis was then explored through additional deletion and mutation in HPV/ tobacco etiological groups, followed byclinico-pathological correlation. In basal/parabasal layer, the molecular signature of the genes was low protein expression/ high promoter methylation of RBSP3, high expression/ low methylation of LIMD1 and high expression of CDC25A. Dysplastic epithelium maintained the signature of RBSP3 through high methylation/ additional deletion with loss of the signatures of LIMD1 and CDC25A via deletion/ additional methylation. Similarly, maintenance and / or loss of signature in invasive tumors was by recurrent deletion/ methylation. Thus, differential patterns of alteration of the genes might be pre-requisite for the development of dysplastic and invasive lesions. Etiological factors played a key role in promoting genetic alterations and determining prognosis. Tobacco negative HNSCC patients had significantly lower alterations of LIMD1 and CDC25A, along with better survival among tobacco negative/ HPV positive patients. Our data suggests the necessity for perturbation of normal molecular profile of RBSP3, LIMD1 and CDC25A in conjunction with etiological factors for head and neck tumorigenesis, implying their diagnostic and prognostic significance.

Combining differential expression, chromosomal and pathway analyses for the molecular characterization of renal cell carcinoma

PubMed Central

Furge, Kyle A; Dykema, Karl; Petillo, David; Westphal, Michael; Zhang, Zhongfa; Kort, Eric J; Teh, Bin Tean

2007-01-01

Using high-throughput gene-expression profiling technology, we can now gain a better understanding of the complex biology that is taking place in cancer cells. This complexity is largely dictated by the abnormal genetic makeup of the cancer cells. This abnormal genetic makeup can have profound effects on cellular activities such as cell growth, cell survival and other regulatory processes. Based on the pattern of gene expression, or molecular signatures of the tumours, we can distinguish or subclassify different types of cancers according to their cell of origin, behaviour, and the way they respond to therapeutic agents and radiation. These approaches will lead to better molecular subclassification of tumours, the basis of personalized medicine. We have, to date, done whole-genome microarray gene-expression profiling on several hundreds of kidney tumours. We adopt a combined bioinformatic approach, based on an integrative analysis of the gene-expression data. These data are used to identify both cytogenetic abnormalities and molecular pathways that are deregulated in renal cell carcinoma (RCC). For example, we have identified the deregulation of the VHL-hypoxia pathway in clear-cell RCC, as previously known, and the c-Myc pathway in aggressive papillary RCC. Besides the more common clear-cell, papillary and chromophobe RCCs, we are currently characterizing the molecular signatures of rarer forms of renal neoplasia such as carcinoma of the collecting ducts, mixed epithelial and stromal tumours, chromosome Xp11 translocations associated with papillary RCC, renal medullary carcinoma, mucinous tubular and spindle-cell carcinoma, and a group of unclassified tumours. Continued development and improvement in the field of molecular profiling will better characterize cancer and provide more accurate diagnosis, prognosis and prediction of drug response. PMID:18542781

Analysis of physiological and miRNA responses to Pi deficiency in alfalfa (Medicago sativa L.).

PubMed

Li, Zhenyi; Xu, Hongyu; Li, Yue; Wan, Xiufu; Ma, Zhao; Cao, Jing; Li, Zhensong; He, Feng; Wang, Yufei; Wan, Liqiang; Tong, Zongyong; Li, Xianglin

2018-03-01

The induction of miR399 and miR398 and the inhibition of miR156, miR159, miR160, miR171, miR2111, and miR2643 were observed under Pi deficiency in alfalfa. The miRNA-mediated genes involved in basic metabolic process, root and shoot development, stress response and Pi uptake. Inorganic phosphate (Pi) deficiency is known to be a limiting factor in plant development and growth. However, the underlying miRNAs associated with the Pi deficiency-responsive mechanism in alfalfa are unclear. To elucidate the molecular mechanism at the miRNA level, we constructed four small RNA (sRNA) libraries from the roots and shoots of alfalfa grown under normal or Pi-deficient conditions. In the present study, alfalfa plants showed reductions in biomass, photosynthesis, and Pi content and increases in their root-to-shoot ratio and citric, malic, and succinic acid contents under Pi limitation. Sequencing results identified 47 and 44 differentially expressed miRNAs in the roots and shoots, respectively. Furthermore, 909 potential target genes were predicted, and some targets were validated by RLM-RACE assays. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed prominent enrichment in signal transducer activity, binding and basic metabolic pathways for carbohydrates, fatty acids and amino acids; cellular response to hormone stimulus and response to auxin pathways were also enriched. qPCR results verified that the differentially expressed miRNA profile was consistent with sequencing results, and putative target genes exhibited opposite expression patterns. In this study, the miRNAs associated with the response to Pi limitation in alfalfa were identified. In addition, there was an enrichment of miRNA-targeted genes involved in biological regulatory processes such as basic metabolic pathways, root and shoot development, stress response, Pi transportation and citric acid secretion.

Challenges of Translating Basic Research Into Therapeutics: Resveratrol as an Example

PubMed Central

Smoliga, James M.; Vang, Ole

2012-01-01

Basic science literature abounds with molecules that promise to ameliorate almost any disease, from curing cancer to slowing the aging process itself. However, most of these compounds will never even be evaluated in humans, let alone proven effective. Here, we use resveratrol as an example to highlight the enormous difficulties in understanding pharmacokinetics, determining side effects, and, ultimately, establishing mechanisms of action for a natural compound. Despite extensive interest and effort, and continuing promising results from basic science groups, very little is known even today about the effects of resveratrol in humans. Part of the problem is the unattractiveness of natural compounds to large, well-funded companies that could run clinical trials because developing their own molecules affords much greater protection for their intellectual property. In fact, selling unpatentable material motivates smaller nutraceutical companies to complicate the scientific problem even more—each creates its own proprietary blend, making it extremely difficult to compare their data with those of other companies, or of academic labs using pure compounds. But even beyond these problems lies a deeper one; resveratrol, and almost every natural compound, is likely to have many clinically relevant targets with different dose–response profiles, tissue distributions, and modifiers. Tackling this type of problem efficiently, and even beginning to address the spectrum of other molecules with claimed benefits, is likely to require the development of new paradigms and approaches. Examples include better molecular modeling to predict interactions, large-scale screens for toxic or other common effects, affinity-based methods to identify drug-interacting proteins, and better synthesis of existing data, including legislation to promote the release of trial results, and tracking of voluntary supplement usage. The evidence for benefits of resveratrol in humans remains too sparse to be conclusive; yet, the limited data that are available, combined with a growing list of animal studies, provide a strong justification for further study. PMID:21746739

Soft matter food physics--the physics of food and cooking.

PubMed

Vilgis, Thomas A

2015-12-01

This review discusses the (soft matter) physics of food. Although food is generally not considered as a typical model system for fundamental (soft matter) physics, a number of basic principles can be found in the interplay between the basic components of foods, water, oil/fat, proteins and carbohydrates. The review starts with the introduction and behavior of food-relevant molecules and discusses food-relevant properties and applications from their fundamental (multiscale) behavior. Typical food aspects from 'hard matter systems', such as chocolates or crystalline fats, to 'soft matter' in emulsions, dough, pasta and meat are covered and can be explained on a molecular basis. An important conclusion is the point that the macroscopic properties and the perception are defined by the molecular interplay on all length and time scales.

A micromotor based on polymer single crystals and nanoparticles: toward functional versatility

NASA Astrophysics Data System (ADS)

Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.

2014-07-01

We report a multifunctional micromotor fabricated by the self-assembly technique using multifunctional materials, i.e. polymer single crystals and nanoparticles, as basic building blocks. Not only can this micromotor achieve autonomous and directed movement, it also possesses unprecedented functions, including enzymatic degradation-induced micromotor disassembly, sustained release and molecular detection.We report a multifunctional micromotor fabricated by the self-assembly technique using multifunctional materials, i.e. polymer single crystals and nanoparticles, as basic building blocks. Not only can this micromotor achieve autonomous and directed movement, it also possesses unprecedented functions, including enzymatic degradation-induced micromotor disassembly, sustained release and molecular detection. Electronic supplementary information (ESI) available: Experimental section, Fig. S1-S8 and Video S1-S4. See DOI: 10.1039/c4nr02593h

Soft matter food physics—the physics of food and cooking

NASA Astrophysics Data System (ADS)

Vilgis, Thomas A.

2015-12-01

This review discusses the (soft matter) physics of food. Although food is generally not considered as a typical model system for fundamental (soft matter) physics, a number of basic principles can be found in the interplay between the basic components of foods, water, oil/fat, proteins and carbohydrates. The review starts with the introduction and behavior of food-relevant molecules and discusses food-relevant properties and applications from their fundamental (multiscale) behavior. Typical food aspects from ‘hard matter systems’, such as chocolates or crystalline fats, to ‘soft matter’ in emulsions, dough, pasta and meat are covered and can be explained on a molecular basis. An important conclusion is the point that the macroscopic properties and the perception are defined by the molecular interplay on all length and time scales.

Information resources at the National Center for Biotechnology Information.

PubMed Central

Woodsmall, R M; Benson, D A

1993-01-01

The National Center for Biotechnology Information (NCBI), part of the National Library of Medicine, was established in 1988 to perform basic research in the field of computational molecular biology as well as build and distribute molecular biology databases. The basic research has led to new algorithms and analysis tools for interpreting genomic data and has been instrumental in the discovery of human disease genes for neurofibromatosis and Kallmann syndrome. The principal database responsibility is the National Institutes of Health (NIH) genetic sequence database, GenBank. NCBI, in collaboration with international partners, builds, distributes, and provides online and CD-ROM access to over 112,000 DNA sequences. Another major program is the integration of multiple sequences databases and related bibliographic information and the development of network-based retrieval systems for Internet access. PMID:8374583

Atmospheric Propagation

NASA Technical Reports Server (NTRS)

Embleton, Tony F. W.; Daigle, Gilles A.

1991-01-01

Reviewed here is the current state of knowledge with respect to each basic mechanism of sound propagation in the atmosphere and how each mechanism changes the spectral or temporal characteristics of the sound received at a distance from the source. Some of the basic processes affecting sound wave propagation which are present in any situation are discussed. They are geometrical spreading, molecular absorption, and turbulent scattering. In geometrical spreading, sound levels decrease with increasing distance from the source; there is no frequency dependence. In molecular absorption, sound energy is converted into heat as the sound wave propagates through the air; there is a strong dependence on frequency. In turbulent scattering, local variations in wind velocity and temperature induce fluctuations in phase and amplitude of the sound waves as they propagate through an inhomogeneous medium; there is a moderate dependence on frequency.

Fusion gene profile of biphenotypic sinonasal sarcoma: an analysis of 44 cases.

PubMed

Fritchie, Karen J; Jin, Long; Wang, Xiaoke; Graham, Rondell P; Torbenson, Michael S; Lewis, Jean E; Rivera, Michael; Garcia, Joaquin J; Schembri-Wismayer, David J; Westendorf, Jennifer J; Chou, Margaret M; Dong, Jie; Oliveira, Andre M

2016-12-01

Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55%), 15 showed rearrangements of PAX3 without MAML3 involvement (34%), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9%). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined. © 2016 John Wiley & Sons Ltd.

Molecular diversity of the faecal microbiota of Toy Poodles in Japan.

PubMed

Omatsu, Tsutomu; Omura, Miki; Katayama, Yukie; Kimura, Toru; Okumura, Maho; Okumura, Atsushi; Murata, Yoshiteru; Mizutani, Tetsuya

2018-05-18

The intestinal microbiota was revealed with the recent advances in molecular techniques, such as high-throughput sequencing analysis. As a result, the microbial changes are thought to influence the health of humans and animals and such changes are affected by several factors including diet, genetics, age, sex, and diseases. Similar studies are being conducted in dogs, and the knowledge of intestinal microbiota in dogs is expanding. Nonetheless, basic information on intestinal microbiota in dogs is less than that of humans. Our aim was to study toy poodles (n=21), a popular companion dog, in terms of basic characteristics of the faecal microbiota by 16S rRNA gene barcoding analysis. In the faecal microbiota, Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria were the dominant phyla (over 93.4% of faecal microbiota) regardless of the attributes of the dogs. In family level, Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae were most prevalent. In case of a dog with protein-losing enteropathy, the diversity of faecal microbiota was different between before and after treatment. This study provides basic information for studying on faecal microbiota in toy poodles.

Zeolitic imidazolate framework-methacrylate composite monolith characterization by inverse gas chromatography.

PubMed

Yusuf, Kareem; Badjah-Hadj-Ahmed, Ahmed Yacine; Aqel, Ahmad; Aouak, Taieb; ALOthman, Zeid Abdullah

2016-04-22

Thermodynamic characterization of butyl methacrylate-co-ethylene dimethacrylate neat monolith and zeolitic imidazolate framework-8 incorporated with butyl methacrylate-co-ethylene dimethacrylate composite monolith were studied using inverse gas chromatography at infinite dilution under 1MPa column pressure and various column temperatures. The free energy of adsorption (ΔGA), enthalpy of adsorption (ΔHA) and entropy of adsorption (ΔSA) were determined using a series of n-alkanes. The dispersive component of surface energy (γS(D)) was estimated by Dorris-Gray and Schultz et al. The composite monolith showed a more energetic surface than the neat monolith. The acidic, KA, and basic, KD, parameters for both materials were estimated using a group of polar probes. A basic character was concluded with more basic behavior for the neat monolith. Flory-Huggins parameter, χ, was taken as a measure of miscibility between the probes with the low molecular weight and the high molecular weight monolith. Inverse gas chromatography provides a better understanding of the role of incorporated zeolitic imidazolate framework (ZIF-8) into the polymer matrix in its monolithic form. Copyright © 2016 Elsevier B.V. All rights reserved.

[Study on action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis based on techniques of gene expression profile and molecular fingerprint].

PubMed

Zhou, Wei; Song, Xiang-gang; Chen, Chao; Wang, Shu-mei; Liang, Sheng-wang

2015-08-01

Action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis were discussed based on gene expression profile and molecular fingerprint in this paper. First, gene expression profiles of atherosclerotic carotid artery tissues and histologically normal tissues in human body were collected, and were screened using significance analysis of microarray (SAM) to screen out differential gene expressions; then differential genes were analyzed by Gene Ontology (GO) analysis and KEGG pathway analysis; to avoid some genes with non-outstanding differential expression but biologically importance, Gene Set Enrichment Analysis (GSEA) were performed, and 7 chemical ingredients with higher negative enrichment score were obtained by Cmap method, implying that they could reversely regulate the gene expression profiles of pathological tissues; and last, based on the hypotheses that similar structures have similar activities, 336 ingredients of compound Danshen dripping pills were compared with 7 drug molecules in 2D molecular fingerprints method. The results showed that 147 differential genes including 60 up-regulated genes and 87 down regulated genes were screened out by SAM. And in GO analysis, Biological Process ( BP) is mainly concerned with biological adhesion, response to wounding and inflammatory response; Cellular Component (CC) is mainly concerned with extracellular region, extracellular space and plasma membrane; while Molecular Function (MF) is mainly concerned with antigen binding, metalloendopeptidase activity and peptide binding. KEGG pathway analysis is mainly concerned with JAK-STAT, RIG-I like receptor and PPAR signaling pathway. There were 10 compounds, such as hexadecane, with Tanimoto coefficients greater than 0.85, which implied that they may be the active ingredients (AIs) of compound Danshen dripping pills in treatment of carotid atherosclerosis (CAs). The present method can be applied to the research on material base and molecular action mechanism of TCM.

General morphological and biological features of neoplasms: integration of molecular findings.

PubMed

Diaz-Cano, S J

2008-07-01

This review highlights the importance of morphology-molecular correlations for a proper implementation of new markers. It covers both general aspects of tumorigenesis (which are normally omitted in papers analysing molecular pathways) and the general mechanisms for the acquired capabilities of neoplasms. The mechanisms are also supported by appropriate diagrams for each acquired capability that include overlooked features such as mobilization of cellular resources and changes in chromatin, transcription and epigenetics; fully accepted oncogenes and tumour suppressor genes are highlighted, while the pathways are also presented as activating or inactivating with appropriate colour coding. Finally, the concepts and mechanisms presented enable us to understand the basic requirements for the appropriate implementation of molecular tests in clinical practice. In summary, the basic findings are presented to serve as a bridge to clinical applications. The current definition of neoplasm is descriptive and difficult to apply routinely. Biologically, neoplasms develop through acquisition of capabilities that involve tumour cell aspects and modified microenvironment interactions, resulting in unrestricted growth due to a stepwise accumulation of cooperative genetic alterations that affect key molecular pathways. The correlation of these molecular aspects with morphological changes is essential for better understanding of essential concepts as early neoplasms/precancerous lesions, progression/dedifferentiation, and intratumour heterogeneity. The acquired capabilities include self-maintained replication (cell cycle dysregulation), extended cell survival (cell cycle arrest, apoptosis dysregulation, and replicative lifespan), genetic instability (chromosomal and microsatellite), changes of chromatin, transcription and epigenetics, mobilization of cellular resources, and modified microenvironment interactions (tumour cells, stromal cells, extracellular, endothelium). The acquired capabilities defining neoplasms are the hallmarks of cancer, but they also comprise useful tools to improve diagnosis and prognosis, as well as potential therapeutic targets. The application of these concepts in oncological pathology leads to consideration of the molecular test requirements (Molecular Test Score System) for reliable implementation; these requirements should cover biological effects, molecular pathway, biological validation, and technical validation. Sensible application of molecular markers in tumour pathology always needs solid morphological support.

Pressure-induced orientational glass phase in molecular para-hydrogen.

PubMed

Schelkacheva, T I; Tareyeva, E E; Chtchelkatchev, N M

2009-02-01

We propose a theoretical description of a possible orientational glass transition in solid molecular para-hydrogen and ortho-deuterium under pressure supposing that they are mixtures of J=0 and J=2 states of molecules. The theory uses the basic concepts and methods of standard spin-glass theory. We expect our orientational glass to correspond to the II' phase of the high-pressure hydrogen phase diagram.

Primer on Molecular Genetics; DOE Human Genome Program

DOE R&D Accomplishments Database

1992-04-01

This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

GENE EXPRESSION PATTERNS ASSOCIATED WITH INFERTILITY IN HUMAN AND RODENT MODELS

EPA Science Inventory

Modern genomic technologies such as DNA arrays provide the means to investigate molecular interactions at an unprecedented level, and arrays have been used to carry out gene expression profiling as a means of identifying candidate genes involved in molecular mechanisms underlying...

Molecular profile of the unique species of traditional Chinese medicine, Chinese seahorse (Hippocampus kuda Bleeker).

PubMed

Zhang, Ning; Xu, Bin; Mou, Chunyan; Yang, Wenli; Wei, Jianwen; Lu, Liang; Zhu, Junjie; Du, Jingchun; Wu, Xiaokun; Ye, Lanting; Fu, Zhiyan; Lu, Yang; Lin, Jianghai; Sun, Zizi; Su, Jing; Dong, Meiling; Xu, Anlong

2003-08-28

A cDNA library of male Chinese seahorse (Hippocampus kuda Bleeker) was constructed to investigate the molecular profile of seahorse as one of the most famous traditional Chinese medicine materials, and to reveal immunological and physiological mechanisms of seahorse as one of the most primitive vertebrates at molecular level. A total of 3372 expressed sequence tags (ESTs) consisting of 1911 unique genes (345 clusters and 1566 singletons) were examined in the present study. Identification of the genes related to immune system, paternal brooding and physiological regulation provides not only valuable insights into the molecular mechanism of immune system in teleost fish but also plausible explanations for pharmacological activities of Chinese seahorse. Furthermore, the occurrence of high prevalent C-type lectins suggested that a lectin-complement pathway might exert a more dominant function in the innate immune system of teleost than mammal. Carbohydrate recognition domain (CRD) without a collagen-like region in the lectins of seahorse was likely an ancient characteristic of lectins similar to invertebrates.

Molecular profiling of multiple myeloma: from gene expression analysis to next-generation sequencing.

PubMed

Agnelli, Luca; Tassone, Pierfrancesco; Neri, Antonino

2013-06-01

Multiple myeloma is a fatal malignant proliferation of clonal bone marrow Ig-secreting plasma cells, characterized by wide clinical, biological, and molecular heterogeneity. Herein, global gene and microRNA expression, genome-wide DNA profilings, and next-generation sequencing technology used to investigate the genomic alterations underlying the bio-clinical heterogeneity in multiple myeloma are discussed. High-throughput technologies have undoubtedly allowed a better comprehension of the molecular basis of the disease, a fine stratification, and early identification of high-risk patients, and have provided insights toward targeted therapy studies. However, such technologies are at risk of being affected by laboratory- or cohort-specific biases, and are moreover influenced by high number of expected false positives. This aspect has a major weight in myeloma, which is characterized by large molecular heterogeneity. Therefore, meta-analysis as well as multiple approaches are desirable if not mandatory to validate the results obtained, in line with commonly accepted recommendation for tumor diagnostic/prognostic biomarker studies.

Free-Energy Profiles of Membrane Insertion of the M2 Transmembrane Peptide from Influenza A Virus

DTIC Science & Technology

2008-12-01

ABSTRACT The insertion of the M2 transmembrane peptide from influenza A virus into a membrane has been studied with molecular - dynamics simulations ...performed replica-exchange molecular - dynamics simulations with umbrella-sampling techniques to characterize the probability distribution and conformation...atomic- detailed molecular dynamics (MD) simulation techniques represent a valuable complementary methodology to inves- tigate membrane-insertion of

PULMONARY GENE EXPRESSION PROFILES OF SPONTANEOUSLY HYPERTENSIVE RATS EXPOSED TO ENVIRONMENTAL TOBACCO SMOKE (ETS)

EPA Science Inventory

Global gene expression profile analysis can be utilized to derive molecular footprints to understand biochemical

pathways implicated in the origin and progression of disease. Functional genomics efforts with tissue-specific focused

genearray appears to be the most...

Strategic placement of stereogenic centers in molecular materials for second harmonic generation.

PubMed

Gangopadhyay, P; Rao, D Narayana; Agranat, Israel; Radhakrishnan, T P

2002-01-01

Basic aspects of the nonlinear optical phenomenon of second harmonic generation (SHG) and the assembly of molecular materials for SHG are reviewed. Extensive use of chirality as a convenient tool to generate noncentrosymmetricity in molecular lattices, an essential requirement for the development of quadratic nonlinear optical materials, is noted. An overview of our investigations of chiral diaminodicyanoquinodimethanes is presented, which provides insight into a systematic approach to the effective deployment of chirality to achieve optimal molecular orientations for enhanced solid state SHG. Extension of these ideas to the realization of strong SHG in materials based on helical superstructures is outlined.

Goals and objectives for molecular pathology education in residency programs. The Association for Molecular Pathology Training and Education Committee.

PubMed

1999-11-01

Increasing knowledge of the molecular basis of disease and advances in technology for analyzing nucleic acids and gene products are changing pathology practice. The explosion of information regarding inherited susceptibility to disease is an important aspect of this transformation. Pathology residency programs are incorporating molecular pathology education into their curricula to prepare newly trained pathologists for the future, yet little guidance has been available regarding the important components of molecular pathology training. We present general goals for pathology training programs for molecular pathology education. These include recommendations to pathology residents for the acquisition of both basic knowledge in human genetics and molecular biology and specific skills relevant to microbiology, molecular oncology, genetics, histocompatibility, and identity determination. The importance of residents gaining facility in integrating data gained via nucleic acid based-technology with other laboratory and clinical information available in the care of patients is emphasized.

Transcriptional profile of human macrophages stimulated by ultra-high molecular weight polyethylene particulate debris of orthopedic implants uncovers a common gene expression signature of rheumatoid arthritis.

PubMed

Terkawi, Mohamad Alaa; Hamasaki, Masanari; Takahashi, Daisuke; Ota, Masahiro; Kadoya, Ken; Yutani, Tomoyo; Uetsuki, Keita; Asano, Tsuyoshi; Irie, Tohru; Arai, Ryuta; Onodera, Tomohiro; Takahata, Masahiko; Iwasaki, Norimasa

2018-01-01

Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process that occurs when host macrophages recognize implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made in understanding the molecular responses of macrophages to implant particles, the pathways/signals that initiate osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanisms in the pathogenesis of osteolysis and aid the identification of molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to ultra-high molecular weight polyethylene (UHMWPE) particles, the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, tumor necrosis factor superfamily member 15 (TNFSF15) and chemokine ligand 20 (CCL20) were further characterized as molecular targets involved in the pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implants and bone tissues. Implant loosening due to osteolysis is the most common mode of arthroplasty failure and represents a great challenge to orthopedic surgeons and a significant economic burden for patients and healthcare services worldwide. Bone loss secondary to a local inflammatory response initiated by particulate debris from implants is considered the principal feature of the pathogenesis of osteolysis. In the present study, we analyzed the transcriptional profiling of human macrophages exposed to UHMWPE particles and identified a large number of inflammatory genes that were not identified previously in macrophage responses to wear particles. Our data provide a new insight into the molecular pathogenesis of osteolysis and highlights a number of molecular targets with prognostic and therapeutic implications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Seeking Optimal Nutrition for Healthy Body Mass Reduction among Former Athletes

PubMed Central

Maciejewska, Dominika; Michalczyk, Małgorzata; Czerwińska-Rogowska, Maja; Banaszczak, Marcin; Ryterska, Karina; Jakubczyk, Karolina; Piotrwski, Jakub; Hołowko, Joanna; Drozd, Arleta; Wysokińki, Paweł; Ficek, Krzysztof; Wilk, Krzysztof; Lubkowska, Anna; Cięszczyk, Paweł; Bertrand, Jerzy

2017-01-01

Abstract The aim of the study was to investigate the efficacy of 6 week Mediterranean diet or 30% calorie restriction on the fatty acid profile and eicosanoids (hydroxyoctadecadienoi acids and hydroxyeicosatetraenoic acids) concentration. Furthermore, basic biochemical variables such as insulin, glucose, HOMA-IR, and a lipid profile were estimated. The study enrolled 94 Caucasian former athletes aged 20-42, with body height of 179 ± 16.00 cm and body mass of 89.26 ± 13.25 kg who had not been active for at least 5 years. The subjects were randomly assigned to one of the three intervention groups: CR group – the 30% calorie restriction (n = 32), MD group - the Mediterranean diet (n = 34), and C group - a control group (n = 28). The pattern of nutrition was analysed before and after the experiment using the 72 h food diaries. In order to evaluate the effect of diet intervention, the following variables were measured: anthropometrics, basic biochemical variables (insulin, fasting glucose, HOMA-IR, lipid profile), fatty acids and their blood derivatives profiles. The CR group showed significantly lower levels of several biochemical variables, i.e., BMI, total cholesterol LDL, TG, total lipids, insulin and HOMA – IR (p < 0.05). Subjects consuming the MD diet significantly decreased their BMI and reduced the level of total lipids (p < 0.05). We did not find any significant changes in the C group. The analysis of the fatty acid profile revealed that the CR group had a significantly decreased EPA level (p < 0.05). The MD group showed a significantly increased level of the DHA (p < 0.05) and improvement in the omega - 3 index (p < 0.05). Subjects following the MD also showed significantly lower concentrations of 15 - hydroxyicosatetraenoic acid (15-HETE). We did not observe any significant differences between the CR and C groups. Within short time, calorie restriction helps to improve lipid variables and insulin resistance. The MD diet seems to be more advantageous in the decrease of inflammation, but does not improve basic biochemical variables. We can conclude that calorie restriction can be a good choice for former athletes, although EPA and DHA supplementation is needed. PMID:29339986

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

AV-USA 1971. Basic Report.

ERIC Educational Resources Information Center

Hope, Thomas W.

Sales analyses, market profiles, discussions of business trends and corporate structures, and a review of new products in the field of audiovisual aids are presented in this report, covering the time span from January 1970 to June 1971. (JY)

A New Maximum Likelihood Approach for Free Energy Profile Construction from Molecular Simulations

PubMed Central

Lee, Tai-Sung; Radak, Brian K.; Pabis, Anna; York, Darrin M.

2013-01-01

A novel variational method for construction of free energy profiles from molecular simulation data is presented. The variational free energy profile (VFEP) method uses the maximum likelihood principle applied to the global free energy profile based on the entire set of simulation data (e.g from multiple biased simulations) that spans the free energy surface. The new method addresses common obstacles in two major problems usually observed in traditional methods for estimating free energy surfaces: the need for overlap in the re-weighting procedure and the problem of data representation. Test cases demonstrate that VFEP outperforms other methods in terms of the amount and sparsity of the data needed to construct the overall free energy profiles. For typical chemical reactions, only ~5 windows and ~20-35 independent data points per window are sufficient to obtain an overall qualitatively correct free energy profile with sampling errors an order of magnitude smaller than the free energy barrier. The proposed approach thus provides a feasible mechanism to quickly construct the global free energy profile and identify free energy barriers and basins in free energy simulations via a robust, variational procedure that determines an analytic representation of the free energy profile without the requirement of numerically unstable histograms or binning procedures. It can serve as a new framework for biased simulations and is suitable to be used together with other methods to tackle with the free energy estimation problem. PMID:23457427

Northwest Latinos' health promotion lifestyle profiles according to diabetes risk status.

PubMed

Sutherland, Leonie L; Weiler, Dawn M; Bond, Laura; Simonson, Shawn; Reis, Janet

2012-12-01

A sample of 225 low income and low education, middle aged Latinos with concern about diabetes and living in a mid-size Idaho city volunteered for a physical assessment for risk status for the disease. The health promoting lifestyles of Latino congregants were measured using the Health Promoting Lifestyle Profile II. Diabetes risk was measured by clinically standard glycated hemoglobin readings. From no risk for the disease to full blown diabetes as determined by glycated hemoglobin levels, the respondents reported engaging in basically the same levels of physical activity, monitoring of nutrition and use of health care services thus evidencing no apparent understanding of the role of lifestyle in disease management. The findings point to the imperative of a broad, comprehensive and especially culturally attuned educational campaign on basic disease pathophysiology, the value of prevention for individual health, and the necessity of day-to-day self-care should diabetes be diagnosed.

Effects of achievement contexts on the meaning structure of emotion words.

PubMed

Gentsch, Kornelia; Loderer, Kristina; Soriano, Cristina; Fontaine, Johnny R J; Eid, Michael; Pekrun, Reinhard; Scherer, Klaus R

2018-03-01

Little is known about the impact of context on the meaning of emotion words. In the present study, we used a semantic profiling instrument (GRID) to investigate features representing five emotion components (appraisal, bodily reaction, expression, action tendencies, and feeling) of 11 emotion words in situational contexts involving success or failure. We compared these to the data from an earlier study in which participants evaluated the typicality of features out of context. Profile analyses identified features for which typicality changed as a function of context for all emotion words, except contentment, with appraisal features being most frequently affected. Those context effects occurred for both hypothesised basic and non-basic emotion words. Moreover, both data sets revealed a four-dimensional structure. The four dimensions were largely similar (valence, power, arousal, and novelty). The results suggest that context may not change the underlying dimensionality but affects facets of the meaning of emotion words.

Nanotechnology Review: Molecular Electronics to Molecular Motors

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Saini, Subhash (Technical Monitor)

1998-01-01

Reviewing the status of current approaches and future projections, as already published in scientific journals and books, the talk will summarize the direction in which computational and experimental nanotechnologies are progressing. Examples of nanotechnological approaches to the concepts of design and simulation of carbon nanotube based molecular electronic and mechanical devices will be presented. The concepts of nanotube based gears and motors will be discussed. The above is a non-technical review talk which covers long term precompetitive basic research in already published material that has been presented before many US scientific meeting audiences.

Molecular Foundry Workshop draws overflow crowd to BerkeleyLab

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Art

2002-11-27

Nanoscale science and technology is now one of the top research priorities in the United States. With this background, it is no surprise that an overflow crowd or more than 350 registrants filled two auditoriums to hear about and contribute ideas for the new Molecular Foundry during a two-day workshop at the Lawrence Berkeley National Laboratory (Berkeley Lab). Scheduled to open for business at Berkeley Labin early 2006, the Molecular Foundry is one of three Nanoscale Science Research Centers (NSRCs) put forward for funding by the DOE's Office of Basic Energy Sciences (BES).

Protection of temperature sensitive biomedical products using molecular alloys as phase change material.

PubMed

Mondieig, Denise; Rajabalee, Fazil; Laprie, Alain; Oonk, Harry A J; Calvet, Thereza; Cuevas-Diarte, Miguel Angel

2003-04-01

In this paper we present an example of the application of molecular alloys for thermal protection of biomedical products during transport or storage. Particularly, thermal protection of blood elements have been considered at different temperatures. All steps from basic research to marketing have been addressed. The high latent heat of fusion of the components allows us to propose molecular alloys as materials for thermal energy storage and also for thermal protection over a large range of temperatures, which can be used in many industrial sectors.

Molecular typing of Salmonella enterica serovar typhi isolates from various countries in Asia by a multiplex PCR assay on variable-number tandem repeats.

PubMed

Liu, Yichun; Lee, May-Ann; Ooi, Eng-Eong; Mavis, Yeo; Tan, Ai-Ling; Quek, Hung-Hiang

2003-09-01

A multiplex PCR method incorporating primers flanking three variable-number tandem repeat (VNTR) loci (arbitrarily labeled TR1, TR2, and TR3) in the CT18 strain of Salmonella enterica serovar Typhi has been developed for molecular typing of S. enterica serovar Typhi clinical isolates from several Asian countries, including Singapore, Indonesia, India, Bangladesh, Malaysia, and Nepal. We have demonstrated that the multiplex PCR could be performed on crude cell lysates and that the VNTR banding profiles produced could be easily analyzed by visual inspection after conventional agarose gel electrophoresis. The assay was highly discriminative in identifying 49 distinct VNTR profiles among 59 individual isolates. A high level of VNTR profile heterogeneity was observed in isolates from within the same country and among countries. These VNTR profiles remained stable after the strains were passaged extensively under routine laboratory culture conditions. In contrast to the S. enterica serovar Typhi isolates, an absence of TR3 amplicons and a lack of length polymorphisms in TR1 and TR2 amplicons were observed for other S. enterica serovars, such as Salmonella enterica serovar Typhimurium, Salmonella enterica serovar Enteritidis, and Salmonella enterica serovar Paratyphi A, B, and C. DNA sequencing of the amplified VNTR regions substantiated these results, suggesting the high stability of the multiplex PCR assay. The multiplex-PCR-based VNTR profiling developed in this study provides a simple, rapid, reproducible, and high-resolution molecular tool for the epidemiological analysis of S. enterica serovar Typhi strains.

Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement

PubMed Central

Brem, Harold; Stojadinovic, Olivera; Diegelmann, Robert F; Entero, Hyacinth; Lee, Brian; Pastar, Irena; Golinko, Michael; Rosenberg, Harvey; Tomic-Canic, Marjana

2007-01-01

Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients’ wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious. PMID:17515955